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1.
Isr Med Assoc J ; 23(9): 563-568, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34472231

RESUMO

BACKGROUND: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts. OBJECTIVES: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding. METHODS: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26-33 weeks gestation) were randomized 1:1 to receive insulin 400 µU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels. RESULTS: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59-8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20-9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29-2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group. CONCLUSIONS: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26-33 weeks.


Assuntos
Nutrição Enteral/estatística & dados numéricos , Hipoglicemiantes/administração & dosagem , Recém-Nascido Prematuro , Insulina/administração & dosagem , Glicemia/efeitos dos fármacos , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Hipoglicemiantes/efeitos adversos , Recém-Nascido , Insulina/efeitos adversos , Masculino , Fatores de Tempo
2.
Lancet Diabetes Endocrinol ; 9(9): 595-605, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34358471

RESUMO

BACKGROUND: Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk. METHODS: In this randomised, double-blind, placebo-controlled, phase 4, single centre trial, we enrolled community-dwelling adults, recruited from the University of Texas Southwestern Medical Center, with BMI of at least 30 kg/m2 or BMI of at least 27 kg/m2 with metabolic syndrome but without diabetes and randomly assigned them, in a 1:1 ratio, to 40 weeks of treatment with once-daily subcutaneous liraglutide 3·0 mg or placebo, in addition to a 500 kcal deficient diet and guideline-recommended physical activity counselling. The primary endpoint was percentage reduction in visceral adipose tissue (VAT) measured with MRI. All randomly assigned participants with a follow-up imaging assessment were included in efficacy analyses and all participants who received at least one dose of study drug were included in the safety analyses. The trial is registered on ClinicalTrials.gov: NCT03038620. FINDINGS: Between July 20, 2017 and Feb 21, 2020 from 235 participants assessed for eligibility, 185 participants were randomly assigned (n=92 liraglutide, n=93 placebo) and 128 (n=73 liraglutide, n=55 placebo) were included in the final analysis (92% female participants, 37% Black participants, 24% Hispanic participants, mean age 50·2 years (SD 9·4), mean BMI 37·7 kg/m2). Mean change in VAT over median 36·2 weeks was -12·49% (SD 9·3%) with liraglutide compared with -1·63% (SD 12·3%) with placebo, estimated treatment difference -10·86% (95% CI -6·97 to -14·75, p<0·0001). Effects seemed consistent across subgroups of age, sex, race-ethnicity, BMI, and baseline prediabetes. The most frequently reported adverse events were gastrointestinal-related (43 [47%] of 92 with liraglutide and 12 [13%] of 93 with placebo) and upper respiratory tract infections (10 [11%] of 92 with liraglutide and 14 [15%] of 93 with placebo). INTERPRETATION: In adults with overweight or obesity at high cardiovascular disease risk, once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment. Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes. FUNDING: NovoNordisk.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Gordura Intra-Abdominal/efeitos dos fármacos , Liraglutida/administração & dosagem , Obesidade/complicações , Sobrepeso/complicações , Adulto , Composição Corporal , Doenças Cardiovasculares , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
3.
Rev Esp Salud Publica ; 952021 Aug 12.
Artigo em Espanhol | MEDLINE | ID: mdl-34381011

RESUMO

OBJECTIVE: The defined daily dose (DDD) is a measurement unit of drug consumption associated with the Anatomic Therapeutic Chemical (ATC) classification for its use in drug utilization studies. Due to the frequent marketing of pharmaceutical specialties with active ingredients combination, the results of the calculation of DDD product in combination with several active ingredients may vary depending on various possible calculation methods. The aim of this study was to compare different ways to calculate DDD of two groups of drugs that included monodrugs as well as combined products. METHODS: From the prescription billing data during 2019 in Catalonia, the results obtained by three methods when calculating the DDDs of non-insulin hypoglycaemic drugs (nIHG) and drugs used in obstructive respiratory pathology (ORP) were compared. The three methods used were the reference calculation provided by the World Health Organization, the calculation of the considered main ingredient and the individualized calculation of all active ingredients of the combination. These methods were compared using the Wilcoxon test for paired data. RESULTS: The results obtained showed high differences both in the total DDD and in the percentage of participation of each pharmacological subgroup within the studied groups. Differences of 17% were observed in nIHG, and of 118% in ORP drugs. The calculation system that takes into account all the active ingredients of the combinations gives a more approximate idea of the total drug consumption, as well as the relative weight of each subgroup. CONCLUSIONS: The calculation of all the active ingredients included in the specialties with drug combinations seems to be the one that can be most useful in pharmacoepidemiological management scenarios such as those in our environment.


Assuntos
Combinação de Medicamentos , Cálculos da Dosagem de Medicamento , Preparações Farmacêuticas , Humanos , Hipoglicemiantes/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Espanha , Organização Mundial da Saúde
4.
Lancet ; 398(10300): 583-598, 2021 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-34370970

RESUMO

BACKGROUND: Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist under development for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of tirzepatide versus titrated insulin degludec in people with type 2 diabetes inadequately controlled by metformin with or without SGLT2 inhibitors. METHODS: In this open-label, parallel-group, multicentre (122 sites), multinational (13 countries), phase 3 study, eligible participants (aged ≥18 years) had a baseline glycated haemoglobin (HbA1c) of 7·0-10·5%, body-mass index of at least 25 kg/m2, stable weight, and were insulin-naive and treated with metformin alone or in combination with an SGLT2 inhibitor for at least 3 months before screening. Participants were randomly assigned (1:1:1:1), using an interactive web-response system, to once-weekly subcutaneous injection of tirzepatide (5, 10, or 15 mg) or once-daily subcutaneous injection of titrated insulin degludec, and were stratified by country, HbA1c, and concomitant use of oral antihyperglycaemic medications. Tirzepatide was initially given at 2·5 mg and the dose was escalated by 2·5 mg every 4 weeks until the assigned dose was reached. Insulin degludec was initially given at 10 U per day and was titrated once weekly to a fasting self-monitored blood glucose of less than 5·0 mmol/L (<90 mg/dL), following a treat-to-target algorithm, for 52 weeks. The primary efficacy endpoint was non-inferiority of tirzepatide 10 mg or 15 mg, or both, versus insulin degludec in mean change from baseline in HbA1c at week 52. Key secondary efficacy endpoints were non-inferiority of tirzepatide 5 mg versus insulin degludec in mean change from baseline in HbA1c at week 52, superiority of all doses of tirzepatide versus insulin degludec in mean change from baseline in HbA1c and bodyweight, and the proportion of participants achieving HbA1c of less than 7·0% (<53 mmol/mol) at week 52. We used a boundary of 0·3% to establish non-inferiority in HbA1c difference between treatments. Efficacy and safety analyses were assessed in the modified intention-to-treat population (all participants who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, number NCT03882970, and is complete. FINDINGS: Between April 1 and Nov 15, 2019, we assessed 1947 participants for eligibility, 1444 of whom were randomly assigned to treatment. The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups. From a mean baseline HbA1c of 8·17% (SD 0·91), the reductions in HbA1c at week 52 were 1·93% (SE 0·05) for tirzepatide 5 mg, 2·20% (0·05) for tirzepatide 10 mg, and 2·37% (0·05) for tirzepatide 15 mg, and 1·34% (0·05) for insulin degludec. The non-inferiority margin of 0·3% was met. The estimated treatment difference (ETD) versus insulin degludec ranged from -0·59% to -1·04% for tirzepatide (p<0·0001 for all tirzepatide doses). The proportion of participants achieving a HbA1c of less than 7·0% (<53 mmol/mol) at week 52 was greater (p<0·0001) in all three tirzepatide groups (82%-93%) versus insulin degludec (61%). At week 52, from a baseline of 94·3 kg (SD 20·1), all three tirzepatide doses decreased bodyweight (-7·5 kg to -12·9 kg), whereas insulin degludec increased bodyweight by 2·3 kg. The ETD versus insulin degludec ranged from -9·8 kg to -15·2 kg for tirzepatide (p<0·0001 for all tirzepatide doses). The most common adverse events in tirzepatide-treated participants were mild to moderate gastrointestinal events that decreased over time. A higher incidence of nausea (12-24%), diarrhoea (15-17%), decreased appetite (6-12%), and vomiting (6-10%) was reported in participants treated with tirzepatide than in those treated with insulin degludec (2%, 4%, 1%, and 1%, respectively). Hypoglycaemia (<54 mg/dL or severe) was reported in five (1%), four (1%), and eight (2%) participants on tirzepatide 5, 10, and 15 mg, respectively, versus 26 (7%) on insulin degludec. Treatment discontinuation due to an adverse event was more common in the tirzepatide groups than in the insulin degludec group. Five participants died during the study; none of the deaths were considered by the investigators to be related to the study treatment. INTERPRETATION: In patients with type 2 diabetes, tirzepatide (5, 10, and 15 mg) was superior to titrated insulin degludec, with greater reductions in HbA1c and bodyweight at week 52 and a lower risk of hypoglycaemia. Tirzepatide showed a similar safety profile to that of GLP-1 receptor agonists. FUNDING: Eli Lilly and Company.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/uso terapêutico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Injeções Subcutâneas , Internacionalidade , Masculino , Pessoa de Meia-Idade
5.
Nutrients ; 13(7)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34371883

RESUMO

The aim of the study was to evaluate the overall biohumoral and metabolic effects of a 12-week add-on therapy consisting of a new nutraceutical formulation (BHC) based on berberine, hesperidin, and chromium picolinate in type 2 diabetes mellitus (T2D) patients with suboptimal glycemic compensation receiving metformin. After 12 weeks, participants in the group receiving metformin plus BHC, compared to the group receiving metformin only, saw a significant improvement in their glucose profile, in terms of both glycated hemoglobin (HbA1c) and fasting blood glucose (FBG). Their FBG dropped from 145 ± 20 mg/dL to 128 ± 23 mg/dL (p < 0.01), a decrease of 11.7% compared with the baseline. This decrease differed significantly from the situation in the control arm (p < 0.05). HbA1c decreased by 7.5% from the baseline, from 53.5 ± 4.3 mmol/mol to 49.5 ± 5.1 mmol/mol (p < 0.01), in the group given BHC, while no difference was seen in the control group. Advanced glycation end products (AGEs) and malondialdehyde (MDA) were found to be significantly reduced (p < 0.01) only in the BHC group, from 9.34 ± 7.61 µg/mL to 6.75 ± 6.13 µg/mL, and from 1.7 ± 0.15 µmol/L to 1.4 ± 0.25 µmol/L, respectively. In patients with T2D taking metformin with suboptimal glycemic compensation, adding BHC for 3 months significantly improved glucose control in terms of FBG and HbA1c, and had a positive effect on the lipid peroxidation profile, as indicated by a decrease in AGEs and MDA.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Controle Glicêmico/métodos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Expert Opin Drug Metab Toxicol ; 17(9): 1139-1148, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34289755

RESUMO

BACKGROUND: Oral semaglutide comprises the glucagon-like peptide-1 analog, semaglutide, and sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). Levothyroxine has similar dosing conditions to oral semaglutide. This trial investigated if oral semaglutide co-administered with levothyroxine affects thyroxine (T4) exposure and if multiple placebo tablets co-administered with oral semaglutide affect semaglutide exposure. RESEARCH DESIGN AND METHODS: In this one-sequence crossover trial, 45 healthy subjects received levothyroxine (600 µg single-dose) alone, or with concomitant SNAC 300 mg or concomitant oral semaglutide 14 mg at steady-state. Subjects also received oral semaglutide 14 mg at steady-state alone or with five placebo tablets once-daily for 5 weeks. RESULTS: A 33% increase in total T4 exposure was observed with levothyroxine/oral semaglutide vs levothyroxine alone, but baseline-corrected maximum concentration (Cmax) was unaffected. SNAC alone did not affect total T4 exposure, whereas Cmax was slightly decreased. A 34% decrease in semaglutide exposure was observed when oral semaglutide was co-administered with placebo tablets, and Cmax also decreased. CONCLUSIONS: Levothyroxine pharmacokinetics were influenced by co-administration with oral semaglutide. Monitoring of thyroid parameters should be considered when treating patients with both oral semaglutide and levothyroxine. Oral semaglutide exposure was influenced by co-administration with multiple tablets, which is addressed in the dosing guidance.


Assuntos
Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Tiroxina/administração & dosagem , Administração Oral , Adulto , Estudos Cross-Over , Interações Medicamentosas , Feminino , Peptídeos Semelhantes ao Glucagon/farmacocinética , Peptídeos Semelhantes ao Glucagon/farmacologia , Humanos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Masculino , Comprimidos , Tiroxina/farmacocinética , Tiroxina/farmacologia
7.
Endocrinol Diabetes Metab ; 4(3): e00228, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34268452

RESUMO

Introduction: Severe COVID-19 has been anecdotally associated with high insulin requirements. It has been proposed that this may be driven by a direct diabetogenic effect of the virus that is unique to SARS-CoV-2, but evidence to support this is limited. To explore this, we compared insulin requirements in patients with severe COVID-19 and non-COVID-19 viral pneumonitis. Methods: This is a retrospective cohort study of patients with severe COVID-19 admitted to our intensive care unit between March and June 2020. A historical control cohort of non-COVID-19 viral pneumonitis patients was identified from routinely collected audit data. Results: Insulin requirements were similar in patients with COVID-19 and non-COVID-19 viral pneumonitis after adjustment for pre-existing diabetes and severity of respiratory failure. Conclusions: In this single-centre study, we could not find evidence of a unique diabetogenic effect of COVID-19. We suggest that high insulin requirements in this disease relate to its propensity to cause severe respiratory failure in patients with pre-existing metabolic disease.


Assuntos
COVID-19/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insuficiência Respiratória/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino
8.
Lancet Diabetes Endocrinol ; 9(9): 563-574, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34293304

RESUMO

BACKGROUND: Semaglutide is an effective treatment for type 2 diabetes; however, 20-30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea. METHODS: We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (≥18 years) with inadequately controlled type 2 diabetes (HbA1c 8·0-10·0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2·0 mg or 1·0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA1c (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162. FINDINGS: Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58·0 years [SD 10·0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2·0 mg (n=480 [50%]) or 1·0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2·0 mg group and 471 (98%) in the semaglutide 1·0 mg group completed the trial. Mean baseline HbA1c was 8·9% (SD 0·6; 73·3 mmol/mol [SD 6·9]) and BMI was 34·6 kg/m2 (SD 7·0). Mean change in HbA1c from baseline at week 40 was -2·2 percentage points with semaglutide 2·0 mg and -1·9 percentage points with semaglutide 1·0 mg (estimated treatment difference [ETD] -0·23 percentage points [95% CI -0·36 to -0·11]; p=0·0003; trial product estimand) and -2·1 percentage points with semaglutide 2·0 mg and -1·9 percentage points with semaglutide 1·0 mg (ETD -0·18 percentage points [-0·31 to -0·04]; p=0·0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was -6·9 kg with semaglutide 2·0 mg and -6·0 kg with semaglutide 1·0 mg (ETD -0·93 kg [95% CI -1·68 to -0·18]; p=0·015; trial product estimand) and -6·4 kg with semaglutide 2·0 mg and -5·6 kg with semaglutide 1·0 mg (ETD -0·77 kg [-1·55 to 0·01]; p=0·054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2·0 mg group and 148 [31%] in the 1·0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2·0 mg and 25 (5%) participants given semaglutide 1·0 mg. Three deaths were reported during the trial (one in the semaglutide 1·0 mg group and two in the semaglutide 2·0 mg group). INTERPRETATION: Semaglutide 2·0 mg was superior to 1·0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control. FUNDING: Novo Nordisk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Compostos de Sulfonilureia/administração & dosagem , Resultado do Tratamento
9.
N Engl J Med ; 385(10): 896-907, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215025

RESUMO

BACKGROUND: Four glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown to reduce the risk of adverse cardiovascular events among persons with type 2 diabetes. The effect of an exendin-based GLP-1 receptor agonist, efpeglenatide, on cardiovascular and renal outcomes in patients with type 2 diabetes who are also at high risk for adverse cardiovascular events is uncertain. METHODS: In this randomized, placebo-controlled trial conducted at 344 sites across 28 countries, we evaluated efpeglenatide in participants with type 2 diabetes and either a history of cardiovascular disease or current kidney disease (defined as an estimated glomerular filtration rate of 25.0 to 59.9 ml per minute per 1.73 m2 of body-surface area) plus at least one other cardiovascular risk factor. Participants were randomly assigned in a 1:1:1 ratio to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo. Randomization was stratified according to use of sodium-glucose cotransporter 2 inhibitors. The primary outcome was the first major adverse cardiovascular event (MACE; a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes). RESULTS: A total of 4076 participants were enrolled; 2717 were assigned to receive efpeglenatide and 1359 to receive placebo. During a median follow-up of 1.81 years, an incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) assigned to receive placebo (5.3 events per 100 person-years) (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P<0.001 for noninferiority; P = 0.007 for superiority). A composite renal outcome event (a decrease in kidney function or macroalbuminuria) occurred in 353 participants (13.0%) assigned to receive efpeglenatide and in 250 participants (18.4%) assigned to receive placebo (hazard ratio, 0.68; 95% CI, 0.57 to 0.79; P<0.001). Diarrhea, constipation, nausea, vomiting, or bloating occurred more frequently with efpeglenatide than with placebo. CONCLUSIONS: In this trial involving participants with type 2 diabetes who had either a history of cardiovascular disease or current kidney disease plus at least one other cardiovascular risk factor, the risk of cardiovascular events was lower among those who received weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg than among those who received placebo. (Funded by Sanofi; AMPLITUDE-O ClinicalTrials.gov number, NCT03496298.).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/administração & dosagem , Nefropatias/complicações , Prolina/administração & dosagem , Idoso , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Nefropatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prolina/efeitos adversos
10.
Nutrients ; 13(6)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204042

RESUMO

A randomized, double-blind, placebo-controlled study was conducted with the primary objective of assessing the effect of a natural extract of Sclerocarya birrea on glucose metabolism in subjects with prediabetes. The duration of the study was 90 days. Thirty-three subjects assigned to the experimental group (daily ingestion of 100 mg of the nutraceutical product) and 34 assigned to the placebo group completed the study. There were 36 men and 31 women with a mean age of 32.3 ± 14.1 years. In the area under the curve (AUC) of the oral glucose tolerance test (OGTT), statistically significant decreases in the experimental group at 40 and 90 days as compared with baseline were found, whereas significant changes in the placebo group were not observed. Within-group differences were statistically significant in favor of the experimental group for glucose peak at OGTT, serum insulin, insulin resistance markers, and flow-mediated dilation. Changes in lipid and anthropometric parameters were not observed, although there was a trend for lower cholesterol levels and a decrease in body weight in the experimental group. Decreases in systolic blood pressure were also higher among subjects in the experimental group. This exploratory study confirms the antidiabetic activity of Sclerocarya birrea in prediabetes. Further studies using better measurements of beta-cell function are needed to clarify the underlying mechanisms of the hypoglycemic effect of this natural compound.


Assuntos
Anacardiaceae , Suplementos Nutricionais , Hipoglicemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Estado Pré-Diabético/terapia , Adulto , Área Sob a Curva , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Método Duplo-Cego , Feminino , Teste de Tolerância a Glucose , Controle Glicêmico/métodos , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue
11.
Expert Rev Endocrinol Metab ; 16(4): 181-189, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34096441

RESUMO

Introduction: The COVID-19 pandemic has affected the entire population with the most deleterious effects in elders. Elders, especially those with diabetes, are at the highest risk of COVID-19 related adverse outcomes and mortality. This is usually linked to the comorbidities that accumulate with age, diabetes-related chronic inflammation, and the pandemic's psychosocial effects.Areas covered: We present some approaches to manage these complicated elderly patients with diabetes during the COVID-19 pandemic. In the inpatient setting, we suggest similar (pre-pandemic) glycemic targets and emphasize the importance of using IV insulin and possible use of continuous glucose monitoring to reduce exposure and PPE utilization. Outside the hospital, we recommend optimal glycemic control within the limits imposed by considerations of safety. We also describe the advantages and challenges of using various technological platforms in clinical care.Expert opinion: The COVID-19 pandemic has lifted the veil off serious deficiencies in the infrastructures for care at both the individual level and the population level and also highlighted some of the strengths, all of which affect individuals with diabetes and COVID-19. We anticipate that things will not return to 'normal' after the COVID-19 pandemic has run its course, but rather they will be superseded by 'New Normal.'


Assuntos
COVID-19/psicologia , Diabetes Mellitus/tratamento farmacológico , Inflamação/complicações , Equipamento de Proteção Individual/ética , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Automonitorização da Glicemia/métodos , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/mortalidade , Doença Crônica , Comorbidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Gerenciamento Clínico , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Educação de Pacientes como Assunto/métodos , Equipamento de Proteção Individual/normas , Prevalência , Medição de Risco , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Telemedicina/métodos
12.
Diabetes Metab Syndr ; 15(4): 102174, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34186369

RESUMO

AIMS: To study the feasibility of diabetes education through telemedicine in patients with diabetes mellitus (DM) hospitalized for coronavirus disease 2019 (COVID-19) management. METHODS: This was a prospective study of 100 patients with DM who were admitted in a COVID isolation ward for management of COVID-19. Patients managed with multiple subcutaneous insulin injections were eligible. During teleconsultation, diabetes education including insulin injection technique was given by a diabetes educator via a phone call (audio and video) during hospitalization. They were also re-assessed after 2 weeks of discharge from the hospital via teleconsultation or in-person. RESULTS: Out of 100 patients, 72.0% had prior history of diabetes while 28.0% were newly diagnosed. The median age of our cohort was 56 years and median duration of diabetes was 7.0 years. Telemedicine as a mode of consult for diabetes education was accepted by 96.0% of patients during hospitalization. At 2 weeks' follow-up, 77.0% patients were following insulin instructions correctly and were satisfied with this mode of consultation. CONCLUSION: Diabetes education using telemedicine as a technology is feasible, acceptable, and effective in the management of most patients with DM. Telemedicine appears to be an effective way to replace routine visits in special situations.


Assuntos
COVID-19/complicações , Diabetes Mellitus/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Insulina/administração & dosagem , Consulta Remota/métodos , SARS-CoV-2/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/transmissão , COVID-19/virologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Nat Med ; 27(6): 1079-1087, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34127852

RESUMO

Agonism of the glucagon-like peptide-1 receptor (GLP-1R) results in glycemic lowering and body weight loss and is a therapeutic strategy to treat type 2 diabetes (T2D) and obesity. We developed danuglipron (PF-06882961), an oral small-molecule GLP-1R agonist and found it had comparable efficacy to injectable peptidic GLP-1R agonists in a humanized mouse model. We then completed a placebo-controlled, randomized, double-blind, multiple ascending-dose phase 1 study ( NCT03538743 ), in which we enrolled 98 patients with T2D on background metformin and randomized them to receive multiple ascending doses of danuglipron or placebo for 28 d, across eight cohorts. The primary outcomes were assessment of adverse events (AEs), safety laboratory tests, vital signs and 12-lead electrocardiograms. Most AEs were mild, with nausea, dyspepsia and vomiting most commonly reported. There were no clinically meaningful AEs in laboratory values across groups. Heart rate generally increased with danuglipron treatment at day 28, but no heart-rate AEs were reported. Systolic blood pressure was slightly decreased and changes in diastolic blood pressure were similar with danuglipron treatment at day 28, compared with placebo. There were no clinically meaningful electrocardiogram findings. In this study in T2D, danuglipron was generally well tolerated, with a safety profile consistent with the mechanism of action of GLP-1R agonism.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Hipoglicemiantes/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/administração & dosagem , Camundongos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/genética , Obesidade/patologia
14.
J Med Chem ; 64(13): 8939-8941, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34133152

RESUMO

Basal glucose control is commonly maintained by a single, once-daily administration of insulin through subcutaneous injection or a continuous pump-infusion. Insulin icodec, a novel ultralong-acting lipidated analog validates the concept of a once-weekly basal injection that is less burdensome, yet equally safe and efficacious as conventional once-daily treatment.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Glicemia , Diabetes Mellitus Tipo 2/metabolismo , Esquema de Medicação , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Infusões Subcutâneas , Insulina/administração & dosagem , Insulina/análogos & derivados
15.
Int J Biol Macromol ; 184: 289-296, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119546

RESUMO

Inhibiting the activity of the intestinal enzyme α-amylase that catalyzes the degradation of starch into glucose can control blood glucose and provide an essential way for the treatment of Type-II diabetes mellitus (T2DM). Here, we compared the structural information of chondroitin sulfate (CS) from different origins and the effects on activity of α-amylase and blood glucose have been investigated. The inhibitory effects of shark and porcine CSs against α-amylase activity is obvious with IC50 values of 11.97 and 14.42 mg/ml, respectively, but the bovine CS almost no effect. From the data of fluorescence spectroscopic analyses, CSs from shark and pig quench Try fluorescence intensity of the enzyme, whereas bovine CS induces an increase. In vivo, oral administration of shark and porcine CSs efficiently suppresses postprandial blood glucose levels in normal and diabetic mice. Our study found that CSs from different sources showed different biological functions even if both molecular weight and disaccharide subunit composition are almost the same, and demonstrated that the CSs from shark and pig as α-amylase inhibitors could be regarded as a novel functional food ingredient in T2DM management.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , alfa-Amilases/antagonistas & inibidores , Administração Oral , Animais , Glicemia/efeitos dos fármacos , Bovinos , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/enzimologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Concentração Inibidora 50 , Masculino , Camundongos , Tubarões , Especificidade da Espécie , Estreptozocina , Suínos , Resultado do Tratamento
16.
J Ayub Med Coll Abbottabad ; 33(2): 188-191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34137526

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive disease due to multiple pathophysiological defects. Monotherapy alone cannot achieve adequate glycemic control and can lead to treatment failure. Empagliflozin, a sodium-glucose cotransporter2 (SGLT2) inhibitor improves glycemic control in patients with T2DM. There were limited studies to determine efficacy and safety profile of empagliflozin with conventional oral antidiabetic drugs (OADs) in Pakistan. So we investigated the efficacy and safety profile of empagliflozin as add-on therapy to metformin and sitagliptin in T2DM patients. METHODS: In this comparative randomized placebo-controlled trial, 240 obese type 2 diabetic patients with inadequate glycaemic control (i.e, HbA1c ≥7%) with metformin and sitagliptin were allocated in to two groups. Patients in group B were given tab empagliflozin 10mg twice a day while patients in group A were given tab placebo for a period of 24 weeks. Changes in body weight, HbA1c, blood pressure were analysed pre and post treatment by using SPSS v23. RESULTS: Empagliflozin caused a significant reduction in body weight -6.9±2.4 kg as compared to placebo -3.1±0.8 kg with p-value <0.001. This body weight reduction was further accompanied by reduction in systolic blood pressure -10.1±2.6 mmHg in empagliflozin group versus -5.3±2.5 mmHg in placebo group with p-value <0.001, and HbA1c -1.68±0.45 in empagliflozin group versus -0.1±0.06 in placebo group with p-value <0.001. There were 28.3% patients in empagliflozin group in whom HbA1c levels reduced <7% as compared to only 13.3% patients in placebo group (p-value 0.04). However no significant adverse effects were recorded in both study groups. CONCLUSIONS: Empagliflozin as a combination therapy has good efficacy and safety profile in obese type 2 diabetic patients.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Obesidade/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adulto , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/farmacologia , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/farmacologia , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Placebos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
17.
N Engl J Med ; 385(6): 503-515, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34170647

RESUMO

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Polipeptídeo Inibidor Gástrico/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Injeções Subcutâneas , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Perda de Peso/efeitos dos fármacos
18.
Expert Rev Clin Pharmacol ; 14(9): 1081-1089, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34015974

RESUMO

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) offer a unique opportunity to simultaneously address various comorbid associated conditions and phenotypic presentations of polycystic ovary syndrome (PCOS) as these agents improve insulin sensitivity, reduce cardiovascular disease (CVD) risk, result in weight loss, and improve nonalcoholic fatty liver disease.Areas covered: The authors describe trials conducted during the last 5 years and provide an update on exenatide and liraglutide use in PCOS women. Information from the studies investigating GLP-1 RAs effects on reducing CVD risk in PCOS is also presented.Expert opinion: Exenatide and liraglutide are good options for the treatment of PCOS when used alone or in combination with metformin. Especially strong consideration should be given to GLP-1 RAs when developing treatment strategies for PCOS women who are overweight or obese, glucose intolerant, have CVD or its attendant risk factors, and/or are seeking treatment for infertility.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/administração & dosagem , Síndrome do Ovário Policístico/tratamento farmacológico , Exenatida/administração & dosagem , Exenatida/farmacologia , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Fatores de Risco de Doenças Cardíacas , Humanos , Hipoglicemiantes/farmacologia , Resistência à Insulina , Liraglutida/administração & dosagem , Liraglutida/farmacologia , Metformina/administração & dosagem , Metformina/farmacologia , Síndrome do Ovário Policístico/fisiopatologia , Perda de Peso/efeitos dos fármacos
19.
J Med Chem ; 64(13): 8942-8950, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-33944562

RESUMO

Here, we describe the molecular engineering of insulin icodec to achieve a plasma half-life of 196 h in humans, suitable for once-weekly subcutaneously administration. Insulin icodec is based on re-engineering of the ultra-long oral basal insulin OI338 with a plasma half-life of 70 h in humans. This systematic re-engineering was accomplished by (1) further increasing the albumin binding by changing the fatty diacid from a 1,18-octadecanedioic acid (C18) to a 1,20-icosanedioic acid (C20) and (2) further reducing the insulin receptor affinity by the B16Tyr → His substitution. Insulin icodec was selected by screening for long intravenous plasma half-life in dogs while ensuring glucose-lowering potency following subcutaneous administration in rats. The ensuing structure-activity relationship resulted in insulin icodec. In phase-2 clinical trial, once-weekly insulin icodec provided safe and efficacious glycemic control comparable to once-daily insulin glargine in type 2 diabetes patients. The structure-activity relationship study leading to insulin icodec is presented here.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Animais , Cães , Esquema de Medicação , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Injeções Intravenosas , Injeções Subcutâneas , Insulina/administração & dosagem , Insulina/análogos & derivados , Masculino , Ratos , Ratos Sprague-Dawley
20.
Diabetes Res Clin Pract ; 176: 108848, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33945841

RESUMO

AIMS: To evaluate efficacy and safety of Gla-300 with Gla-100 in a patient-level meta-analysis among large East Asian patients with type 2 diabetes mellitus (T2DM). METHODS: A patient level meta-analysis of three EDITION studies with similar design and endpoints were conducted over 6-months treatment period. The analysis included 547 patients treated with Gla-300 and 348 patients treated with Gla-100. RESULTS: Over 6-month treatment period, mean change in HbA1c was similar for Gla-300 [Least square (LS) mean, (SE): -1.13 (0.05) % and Gla-100: -1.14 (0.05) %], showing non-inferiority of Gla-300 to Gla-100 (LS mean difference: 0.02%, 95% CI: -0.08 to 0.11). Gla-300 was associated with reduced risk of hypoglycemic event (confirmed ≤ 3.9 mmol/L or severe) vs Gla-100 at any time of day or at night (00:00-05:59 h). The event rates of hypoglycemia were consistently lower with Gla-300 than Gla-100. Severe hypoglycemia was rare in both treatment groups. Weight gain was minimal in both treatment groups. CONCLUSION: Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle Glicêmico/métodos , Insulina Glargina/administração & dosagem , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Relação Dose-Resposta a Droga , Extremo Oriente/etnologia , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/etnologia
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