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1.
Pediatr Endocrinol Diabetes Metab ; 27(2): 134-140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34514769

RESUMO

Metformin is a widely used biguanide drug recommended as a first-line antidiabetic for type 2 diabetes. Currently, metformin is used not only in the treatment of diabetes but also in other diseases. Some studies have shown that metformin causes weight loss in insulin-sensitive and insulin-resistant overweight and obese patients. Metformin is an effective and safe option for women with gestational diabetes and type 2 diabetes in pregnancy, and it may also increase the ovulation rate in patients with polycystic ovary syndrome (PCOS). Longer survival times have been observed in cancer patients using metformin. Metformin has been shown to significantly correlate with lower mortality in obese or type 2 diabetic women hospitalized for COVID-19. It also has a protective effect on the development and progression of many types of cancer. The mechanisms of action of metformin are complex and still not fully understood. Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms. This paper presents the benefits of using metformin in the treatment of various diseases.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Metformina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Gravidez , SARS-CoV-2
2.
Artigo em Inglês | MEDLINE | ID: mdl-34493495

RESUMO

INTRODUCTION: People with type 2 diabetes (T2D) have an increased rate of hospitalization and mortality related to COVID-19. To identify ahead of time those who are at risk of developing severe diseases and potentially in need of intensive care, we investigated the independent associations between longitudinal glycated hemoglobin (HbA1c), the impact of common medications (metformin, insulin, ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and corticosteroids) and COVID-19 severity in people with T2D. RESEARCH DESIGN AND METHODS: Retrospective cohort study was conducted using deidentified claims and electronic health record data from the OptumLabs Data Warehouse across the USA between January 2017 and November 2020, including 16 504 individuals with T2D and COVID-19. A univariate model and a multivariate model were applied to evaluate the association between 2 and 3-year HbA1c average, medication use between COVID-19 diagnosis and intensive care unit admission (if applicable), and risk of intensive care related to COVID-19. RESULTS: With covariates adjusted, the HR of longitudinal HbA1c for risk of intensive care was 1.12 (per 1% increase, p<0.001) and 1.48 (comparing group with poor (HbA1c ≥9%) and adequate glycemic control (HbA1c 6%-9%), p<0.001). The use of corticosteroids and the combined use of insulin and metformin were associated with significant reduction of intensive care risk, while ACEIs and ARBs were not associated with reduced risk of intensive care. CONCLUSIONS: Two to three-year longitudinal glycemic level is independently associated with COVID-19-related severity in people with T2D. Here, we present a potential method to use HbA1c history, which presented a stronger association with COVID-19 severity than single-point HbA1c, to identify in advance those more at risk of intensive care due to COVID-19 in the T2D population. The combined use of metformin and insulin and the use of corticosteroids might be significant to prevent patients with T2D from becoming critically ill from COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Teste para COVID-19 , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Estudos Retrospectivos , SARS-CoV-2
3.
J Coll Physicians Surg Pak ; 31(9): 1035-1039, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34500517

RESUMO

OBJECTIVE: The purpose of the present study was to determine the effects of exenatide treatment on platelet function in type 2 diabetes mellitus (DM) patients. STUDY DESIGN: Case-control observational study. PLACE AND DURATION OF STUDY: University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara from October 2016 to October 2018. METHODOLOGY: This study included 50 patients with type 2 DM, who had started exenatide therapy; and age-gender matched 54 control subjects. The biochemical data and BMI of the patients were analysed at the time of admission and after six months of exenatide treatment. RESULTS: PDW (platelet distribution width) and MPV (mean platelet volume) were higher in the diabetic patient group than in the control group (p <0.01 and p=0.036, respectively). Significant positive correlations were determined between PDW and BMI (p<0.001), FPG (p <0.001), and HbA1c (p<0.001). After six months of exenatide treatment, PDW (p = 0.015) values and platelet count (p = 0.003) were significantly decreased. CONCLUSIONS: Exenatide causes a decrease in PDW value and platelet count independent of its positive effect on lipid profile, glycemic regulation, and weight loss, which contributes to explain the effect of treatment on the cardiovascular system through a different mechanism. Key Words: Exenatide, Type 2 diabetes mellitus, Platelet count, Platelet distribution width, Mean platelet volume.


Assuntos
Diabetes Mellitus Tipo 2 , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Exenatida , Humanos , Volume Plaquetário Médio , Contagem de Plaquetas
4.
West Afr J Med ; 38(8): 756-761, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34503324

RESUMO

BACKGROUND: The use of fixed dose combination oral antidiabetic drugs (OADs) in the therapeutic management of type 2 diabetes mellitus (DM) patients is becoming popular among clinicians. Reduced pill burden with fixed combination OADs is generally perceived to improve adherence and efficacy. The aim of this study was to compare the efficacy, tolerability and side effects (SEs) profile of vildagliptin-metformin (VM) combination with metformin-glibenclamide (MG) combination in type 2 DM patients at the Aminu Kano Teaching Hospital (AKTH). METHODS: A descriptive prospective open-labeled comparative out-patient study of type 2 DM patients spanning over three months with 60 Patients assigned to two treatment groups - VM (Group 1) and MG (Group 2) of 30 patients each. Parameters measured at baseline, 6 weeks and 12 weeks of study included demographic and anthropometric data; fasting plasma glucose (FPG) level; 2-hour post-prandial (2-hrPPG) glucose; liver function tests (LFTs); Electrolyte, Urea and Creatinine (EUCr); and fasting plasma lipids. Glycated haemoglobin (HbA1c) was measured at baseline and at 12 weeks of the study. A p-value of <0.05 was considered to be significant. RESULTS: There was improvement in FPG, 2hr PPG, HbA1c in all subjects in both groups at the end of the study (6.44±0.79mmol/ l, 8.80±1.16mmol/l and 7.22±1.20% respectively in group 1(VM); and 6.40±0.83mmol/l, 9.29±1.39 and 7.25±0.96% respectively for group 2(MG). There was a significant improvement in body mass index (BMI) of subjects in group 1 (30.02±4.16 at baseline, 29.71±4.12 at study end) compared to those in group 2 (31.98±6.32 at baseline, 32.62±6.30 at study end), p=0.04. At the end of the study, the efficacy of VM (HbA1C-7.22±1.20%) was comparable to that of MG (HbA1c-7.25±0.96), P=0.92. The tolerability of MG (attrition rate 6.7%) was better than that of VM (attrition rate 13%), although this difference was not statistically significant P=0.16. The subjects on VM experienced more gastrointestinal (GIT) side effects compared to those on MG. The major SEs experienced by those on MG were hypoglycaemia and weight gain. VM was less tolerated and had more GIT side effects than MG. CONCLUSION: The use of single pill combination oral antidiabetic medications is associated with improved efficacy.


Assuntos
Adamantano , Diabetes Mellitus Tipo 2 , Metformina , Adamantano/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Humanos , Metformina/efeitos adversos , Nigéria , Nitrilas/efeitos adversos , Estudos Prospectivos , Pirrolidinas/efeitos adversos , Vildagliptina/uso terapêutico
5.
BMJ Case Rep ; 14(9)2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34511416

RESUMO

Primary lung abscess as a complication of necrotising community-acquired pneumonia due to multidrug-resistant (MDR) Klebsiella pneumoniae is rare. A 63-year-old man with a medical history of type 2 diabetes mellitus and chronic kidney disease was diagnosed with lung abscess due to MDR Klebsiella pneumoniae, a rare organism as a causative agent for community-acquired pneumonia. This unusual case revealed therapeutic challenges faced owing to factors such as drug-resistant pathogen, longer duration of antibiotics required for lung abscess and the chronic kidney status of the patient limiting the dosage of antibiotics. The clinical nuggets discussed in this case might pave the way in the future for management guidelines to be formulated in optimising the selection and duration of therapy for lung abscesses with MDR aetiology and in early recognition of this rare but dreaded entity.


Assuntos
Infecções Comunitárias Adquiridas , Diabetes Mellitus Tipo 2 , Infecções por Klebsiella , Abscesso Pulmonar , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Abscesso Pulmonar/diagnóstico , Abscesso Pulmonar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
6.
J Assoc Physicians India ; 69(6): 11-12, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34472787

RESUMO

BACKGROUND: The present study intended to estimate the comorbidities and risk factors among patients with hypertension in India. Further, the current practice of hypertension management was evaluated and the choice of therapy was assessed based on hypertension grade, risk factors, and comorbidities. METHODS: Electronic medical record data (June 2017-June 2019) of Indian adult hypertensive patients (≥140/90 mmHg) who had two blood pressure (BP) readings were retrospectively analyzed. Demographic characteristics, BP readings, comorbidities, medications and co-medications, and laboratory data were collected at baseline. Grids based on hypertension grade (I, II, and III), demographic factors, risk factors, and comorbidities were created and prescribed antihypertensive drugs (AHDs) in each grid were evaluated. RESULTS: Among 100,075 patients, the proportion of patients in 18-40 year, 40-65 year, and >65 year age groups were 11.4%, 65.1%, and 23.4%, respectively. Proportion of men and women was similar (52.0% vs 47.9%). Proportion of patients with BMI <25 Kg/m2 was 8.1%, 25-29.9 Kg/m2 was 11.9%, and >30 Kg/m2 was 8.8%. Mean BP of patients with hypertension was: grade I (145.05/90.73 mmHg), grade II (160.07/95.64 mmHg), and grade III (180.82/102.76 mmHg). Mean low density lipoprotein (113.26 mg/dL), serum creatinine (2.28 mg/dL), mean HbA1c (8.7%) levels were highest among patients with grade III hypertension. Commonly observed comorbidities were type 2 diabetes mellitus (T2DM: 51.5%), dyslipidemia (36.4%), and chronic kidney disease (CKD: 4.4%). Top concomitant medications included anti-diabetic therapies (34.6%), drugs for dyslipidemia (30.0%), and anti-platelet therapies (6.9%). CONCLUSION: Most prescribed AHD monotherapies were angiotensin receptor II blockers (ARBs) and calcium channel blockers (CCBs) and most prescribed combination therapies were ARBs + diuretics and ARBs + CCBs. Telmisartan and amlodipine+telmisartan for patients with comorbid T2DM or dyslipidemia and metoprolol for those with coronary artery disease were the commonly prescribed AHDs.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Índia/epidemiologia , Masculino , Morbidade , Estudos Retrospectivos , Fatores de Risco
7.
J Assoc Physicians India ; 69(8): 11-12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34472814

RESUMO

Around 300- 400 AD, ancient Indian physicians described a condition akin to diabetes mellitus which was called "Madhumeha". Sushrutha and Charaka, are also credited with describing two types of diabetes which would roughly correspond to type 1 diabetes and type 2 diabetes. However, little is known about the history of diabetes in India between the first and 19th century AD. A thorough search of literature revealed a large number of publications on diabetes from India in the 1800s and early 1900s, mostly from Calcutta and the Madras Presidency, suggesting that the prevalence of diabetes was high in these two places. Building on the observations made by a number of English physicians, Chunilal Bose in 1907 suggested the link between diabetes and lifestyle in India. Amazingly, India did not have to wait long after the discovery of insulin by Banting and Best at Toronto in 1921, to get its own supply. Around this time, Dr. J.P. Bose, eminent physician and diabetologist from Calcutta made remarkable contributions to the study of diabetes in India. He was also the first to describe the dramatic effects of insulin administration to children with type 1 diabetes in India. All these facts have remained largely forgotten which prompted the authors to delve deep into the history of diabetes in pre-independence India. This has led to the unearthing of several pearls of knowledge which are presented in this article as a fitting tribute to the 100th year of Insulin Discovery.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Médicos , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , História do Século XX , Humanos , Índia/epidemiologia , Insulina , Masculino
11.
J Assoc Physicians India ; 69(4): 11-12, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34470191

RESUMO

The concept of SGLT2-inhibition, once regarded as a non-physiological approach to glycemia control, now finds a foundational relevance in risk-modification for cardiovascular, kidney, and metabolic outcomes, spanning beyond type-2 diabetes. Major studies have proven meaningful improvements in various clinical outcomes, with different SGLT2-i agents. Apart from glycosuria, SGLT2-inhibition is associated with several patho-physiological effects, which may contribute to the clinical benefits seen with these agents. This narrative review is an attempt to appraise the different patho-physiological effects mediated by SGLT2-inhibition, based on contemporary evidence. The review classifies these effects in the acronym of EUPHORIA, and grades the possible relevance of each effect, in improving clinical outcomes.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Euforia , Homeostase , Humanos , Hipoglicemiantes , Transportador 2 de Glucose-Sódio
13.
BMJ Case Rep ; 14(9)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489258

RESUMO

A 62-year-old woman with a history of end-stage renal disease on haemodialysis, essential hypertension and type 2 diabetes mellitus was diagnosed with sepsis and placed on 600 mg oral linezolid every 12 hours and 1 g intravenous ceftriaxone every 24 hours. Blood cultures grew Streptococcus dysgalactiae, and she was switched to intravenous ceftriaxone 2 g daily. Platelet counts slowly trended down after starting ceftriaxone reaching 5 K/µL on day 12 of treatment. Ceftriaxone was discontinued and heparin-induced thrombocytopaenia was ruled out. She was switched to vancomycin and her platelet count improved. Given the temporal relationship between changing platelet counts and starting and discontinuing ceftriaxone, a diagnosis of drug-induced thrombocytopaenia was made.


Assuntos
Diabetes Mellitus Tipo 2 , Preparações Farmacêuticas , Trombocitopenia , Ceftriaxona/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Streptococcus , Trombocitopenia/induzido quimicamente
14.
BMJ Open ; 11(9): e049782, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475174

RESUMO

MAIN OBJECTIVE: To determine how and to what extent COVID-19 has affected real-world, self-reported glycaemic management in Americans with type 1 or type 2 diabetes taking insulin and/or secretagogues, with or without infection. DESIGN: A cross-sectional substudy using data from the Investigating Novel Predictions of Hypoglycemia Occurrence using Real-world Models panel survey. SETTING: USA. PARTICIPANTS: Americans 18-90 years old with type 1 or 2 diabetes taking insulin and/or secretagogues were conveniently sampled from a probability-based internet panel. PRIMARY OUTCOME MEASURE: A structured, COVID-19-specific questionnaire was administered to assess the impact of the pandemic (irrespective of infection) on socioeconomic, behavioural/clinical and psychosocial aspects of glycaemic management. RESULTS: Data from 667 respondents (type 1 diabetes: 18%; type 2 diabetes: 82%) were analysed. Almost 25% reported A1c values ≥8.1%. Rates of severe and non-severe hypoglycaemia were 0.68 (95% CI 0.5 to 0.96) and 2.75 (95% CI 2.4 to 3.1) events per person-month, respectively. Ten respondents reported a confirmed or probable COVID-19 diagnosis. Because of the pandemic, 24% of respondents experienced difficulties affording housing; 28% struggled to maintain sufficient food to avoid hypoglycaemia; and 19% and 17% reported challenges accessing diabetes therapies and testing strips, respectively. Over one-quarter reported issues retrieving antihyperglycaemics from the pharmacy and over one-third reported challenges consulting with diabetes providers. The pandemic contributed to therapeutic non-adherence (14%), drug rationing (17%) and reduced monitoring (16%). Many struggled to keep track, and in control, of hypoglycaemia (12%-15%) and lacked social support to help manage their risk (19%). Nearly half reported decreased physical activity. Few statistically significant differences were observed by diabetes type. CONCLUSIONS: COVID-19 was found to cause substantial self-reported deficiencies in glycaemic management. Study results signal the need for decisive action to restabilise routine diabetes care in the USA. TRIAL REGISTRATION NUMBER: NCT04219514.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste para COVID-19 , Estudos Transversais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Autorrelato , Estados Unidos/epidemiologia , Adulto Jovem
15.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361791

RESUMO

As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions in a personal glucose meter (PGM). α-glucosidase catalyzes the hydrolysis of maltose to produce glucose, which triggers the reduction of ferricyanide (K3[Fe(CN)6]) to ferrocyanide (K4[Fe(CN)6]) and generates the PGM detectable signals. When the α-glucosidase inhibitor (such as acarbose) is added, the yield of glucose and the readout of PGM decreased accordingly. This method can achieve the direct determination of α-glucosidase activity by the PGM as simple as the blood glucose tests. Under the optimal experimental conditions, the developed method was applied to evaluate the inhibitory activity of thirty-four small-molecule compounds and eighteen medicinal plants extracts on α-glucosidase. The results exhibit that lithospermic acid (52.5 ± 3.0%) and protocatechualdehyde (36.8 ± 2.8%) have higher inhibitory activity than that of positive control acarbose (31.5 ± 2.5%) at the same final concentration of 5.0 mM. Besides, the lemon extract has a good inhibitory effect on α-glucosidase with a percentage of inhibition of 43.3 ± 3.5%. Finally, the binding sites and modes of four active small-molecule compounds to α-glucosidase were investigated by molecular docking analysis. These results indicate that the PGM method is feasible to screening inhibitors from natural products with simple and rapid operations.


Assuntos
Benzaldeídos/farmacologia , Benzofuranos/farmacologia , Glicemia/análise , Catecóis/farmacologia , Depsídeos/farmacologia , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores de Glicosídeo Hidrolases/farmacologia , Monitorização Ambulatorial/métodos , alfa-Glucosidases/sangue , Acarbose/química , Acarbose/farmacologia , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Sítios de Ligação , Técnicas Biossensoriais/instrumentação , Catecóis/química , Catecóis/isolamento & purificação , Depsídeos/química , Depsídeos/isolamento & purificação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hidrólise , Cinética , Maltose/metabolismo , Simulação de Acoplamento Molecular , Monitorização Ambulatorial/instrumentação , Extratos Vegetais/química , Plantas Medicinais , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Termodinâmica , Dispositivos Eletrônicos Vestíveis , alfa-Glucosidases/química
16.
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
17.
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
18.
Am J Nurs ; 121(9): 25, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438427

RESUMO

Dapagliflozin (Farxiga) is now approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease with or without type 2 diabetes.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Insuficiência Cardíaca/complicações , Humanos , Nefropatias , Fatores de Tempo
20.
BMJ Case Rep ; 14(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404640

RESUMO

Following non-elective orthopaedic surgery, a 61-year-old man with poorly controlled type 2 diabetes mellitus on empagliflozin developed high anion gap metabolic acidosis in the high-dependency unit. Metabolic acidosis persisted despite intravenous sodium bicarbonate, contributing to tachycardia and a run of non-sustained ventricular tachycardia. He was euglycaemic throughout hospital admission. Investigations revealed elevated urine and capillary ketones, and a diagnosis of sodium-glucose cotransporter-2 inhibitor-associated euglycaemic diabetic ketoacidosis was made. He was treated with an intravenous sliding scale insulin infusion and concurrent dextrose 5% with potassium chloride. Within 24 hours of treatment, his arterial pH, anion gap and serum bicarbonate levels normalised. After a further 12 hours, the intravenous insulin infusion was converted to a basal/bolus regimen of subcutaneous insulin, and he was transferred to the general ward. He was discharged well on subcutaneous insulin 6 days postoperatively.


Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/tratamento farmacológico , Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
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