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1.
Orv Hetil ; 161(5): 193-197, 2020 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-31984772

RESUMO

Mortality in type 1 diabetes, although showing a declining trend, is significantly higher than standard mortality. The case study focuses on a woman who lived for 91 years; she was insulin-dependent for 86 years and has been treated by a single physician - the author - for over 55 years. She was diagnosed with diabetes in 1932 at the age of five. Her diabetes was first treated with rapid-acting insulin three times daily, then from 1940 with rapid-acting and protamine zinc insulin once daily, while later on pork, then human crystalline zinc insulin was used, followed by a mixture of rapid-acting and NPH insulin for the last 16 years. The reason behind the above treatment regimen was that the patient obsessively insisted on a once daily insulin dose and the duration was shown to be 24 hours for each insulin. The continuous overdose of a single insulin for decades has resulted in hypoglycemic episodes almost daily, with consequent high fluctuations in blood glucose levels. She performed urine glucose tests using a polarimeter from the mid-1930s to the sixties, then used test strips until the early eighties, and later switched to blood glucose self-testing. Her HbA1c levels have been around 7% (53 mmol/mol) for the last 25 years. She did not develop retinopathy or nephropathy, only severe neuropathy caused complaints during the last years of her life. In addition, her vision continued to deteriorate due to age-related dry macular degeneration. She is a Joslin 75-year medalist. For the last two months of her life, she gave permission for degludec + glulisine insulin intensive treatment. Her death was caused by myocardial infarction. Although minimizing blood glucose fluctuations and sustaining good metabolic control significantly improve the life expectancy of people with diabetes, in our case neither has existed for well over half a century. Therefore, no explanation was found for the extremely long duration of diabetes and longevity. Orv Hetil. 2020; 161(5): 193-197.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Infarto do Miocárdio/mortalidade , Idoso de 80 Anos ou mais , Glicemia , Evolução Fatal , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Insulina , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Infarto do Miocárdio/complicações , Resultado do Tratamento
2.
Cardiol Rev ; 27(5): 260-266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393288

RESUMO

Long-acting basal insulins are used for the management of both type 1 and type 2 diabetes mellitus. Long-acting basal insulins were developed utilizing recombinant DNA technology and have been available since 2000 with the approval of insulin glargine U-100 followed by insulin detemir in 2005. In recent years, diabetes management has become more complex with the approval of insulin glargine U-300 and insulin degludec U-100 and U-200. Both insulin glargine U-300 and insulin degludec have been compared with insulin glargine U-100 and have demonstrated longer durations of action, as well as lower rates of hypoglycemia. This review discusses the Food and Drug Administration-approved long-acting insulins with a focus on recently approved agents and their efficacy and safety compared with the first long-acting basal insulins.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Guias de Prática Clínica como Assunto , Ensaios Clínicos como Assunto , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Masculino
3.
Endocr J ; 66(8): 745-752, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31308304

RESUMO

To examine the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) or once-daily second-generation basal insulin analogs (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes in routine clinical practice. A 12-week multicenter, open-label, randomized, pilot study was performed in 52 subjects with type 2 diabetes treated with oral antidiabetic drugs (OADs). Subjects were randomized to once-daily IDegAsp (n = 26) or basal insulin (n = 26). The primary endpoint was percent change in HbA1c from baseline to week 12. Furthermore, it was analyzed post hoc in subgroups stratified by baseline HbA1c. During a follow-up period, percent change in HbA1c was not significantly different between the two groups (p = 0.161). Daily insulin doses and frequency of overall hypoglycemia were also similar in the two groups. In post hoc analyses, once-daily basal insulin was more effective than IDegAsp in subjects with HbA1c more than or equal to 8.5% (p < 0.05); however, in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant improvement in percent change in HbA1c at week 12, compared with basal insulin (p < 0.01). Although there was no apparent difference in the HbA1c-lowering effects between two groups, when compared in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant effect in comparison with once-daily basal insulin. These findings suggest that the baseline HbA1c level might provide the important information for choosing IDegAsp or basal insulin in patients insufficiently controlled with OADs. This trial was registered with UMIN (no. UMIN000035431).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Administração Oral , Adulto , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Preparações de Ação Retardada , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Projetos Piloto
4.
Diabetes Res Clin Pract ; 152: 58-64, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31102682

RESUMO

AIM: To report glycemic control and pregnancy outcome in pregnant women with type 1 diabetes on insulin degludec. METHODS: Twenty-two women with type 1 diabetes on degludec from conception to delivery between 2014 and 2018 were compared with 51 pregnant women with type 1 diabetes on glargine. RESULTS: Baseline characteristics were comparable, however HbA1c was higher at median 9 (range 5-19) weeks in women on degludec compared to women on glargine (6.9% (5.7-8.7); (52 (39-72) mmol/mol) versus 6.4% (5.1-10.1); (46 (32-87) mmol/mol), p = 0.04). HbA1c was similar in late pregnancy (6.3% (5.6-7.1); (45 (38-54) mmol/mol) versus 6.1% (5.2-9.0); (43 (33-75) mmol/mol), p = 0.28). The prevalence of severe hypoglycemia was 3 (14%) versus 6 (12%), p = 1.00 during pregnancy and 0 versus 1, p = 1.00 during hospital admittance after delivery. Most women on degludec used one daily injection in early (20 (91%) versus 25 (49%), p = 0.001) and late pregnancy (21 (96%) versus 19 (37%), p < 0.001). No significant differences in obstetrical and neonatal outcomes were found between the groups. Maternal hospital admittance after delivery was 2 (1-5) versus 3 (2-11) days (p = 0.004). CONCLUSIONS: Glycemic control in late pregnancy, severe hypoglycemia during and immediately after pregnancy as well as pregnancy outcome were comparable in women on degludec or glargine. Degludec initiated preconceptionally may be continued in pregnancy.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina de Ação Prolongada/administração & dosagem , Gravidez em Diabéticas/tratamento farmacológico , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Hospitalização/estatística & dados numéricos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez/epidemiologia , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/epidemiologia , Prevalência , Resultado do Tratamento , Adulto Jovem
5.
Acta Diabetol ; 56(9): 973-980, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30945047

RESUMO

Meta-analyses of clinical trials comparing CSII with traditional insulin injections usually show a small, but significant advantage of CSII with respect to HbA1c and risk of severe hypoglycemia. On the other hand, CSII is associated with a small, but relevant risk of ketoacidosis, mainly due to malfunction of insulin pump and/or catheter occlusion. During last time, the technology of insulin pumps and infusion sets has improved as the profound evolution in type and schemes with traditional insulin injections. Aim of the present study is to update previous meta-analyses comparing CSII with traditional insulin injections in subjects with type 1 diabetes. Specific subgroup analyses were designed for assessing the effects of CSII in comparison with basal-bolus MDI, with short-acting analogues as bolus and long-acting analogues as basal insulin. In addition, an exploratory analysis was performed to verify the effect of CSII in insulin-naïve patients with type 1 diabetes. The present analysis includes all randomized clinical trials comparing CSII with traditional injections in type 1 diabetes, with a duration of at least 12 weeks. Animal studies were excluded, whereas no language or date restriction was imposed. If duplicate publications of a single trial were present, the paper containing more adequate information was considered as principal publication. In trials comparing CSII with basal-bolus MDI, performed before the introduction of rapid-acting analogues, regular human insulin was used for CSII, and as prandial insulin in control groups. CSII was associated with a significant reduction of A1c, in comparison with MDI, irrespective of the use of either human insulin or rapid-acting analogues. However, in trials with rapid-acting analogue the advantage of CSII was significantly smaller than in trials with regular human insulin (HbA1c difference: - 0.29[- 0.46; - 0.13] vs - 1.93[- 1.84; - 0.42]%; p = 0.02). Different rapid-acting analogues provided similar results (HbA1c reduction vs MDI: - 0.25 [- 0.48; - 0.02]%, p = 0.03, and - 0.29 [- 0.49; - 0.09]%, p = 0.005, for lispro and aspart, respectively). In addition, in trials comparing CSII with basal-bolus MDI, CSII reduced HbA1c to a similar extent irrespective of the use of either NPH or long-acting analogues as basal insulin in the control groups (HbA1c reduction vs MDI: - 0.31 [- 0.55; - 0.06]%, p = 0.01, and - 0.20 [- 0.38; - 0.03]%, p = 0.02, for NPH and long-acting analogues, respectively. With respect to severe hypoglycemia, CSII did not produce a significant reduction of risk in comparison with traditional insulin injections. Conversely, CSII was associated with a significant increase in the incidence of reported diabetic ketoacidosis (DKA). Notably, the increased risk of DKA was significant in trials comparing CSII with conventional insulin therapy, whereas only a nonsignificant trend toward an increased risk was observed in comparisons with basal-bolus MDI. Only two trials comparing CSII with basal-bolus MDI, both using rapid-acting analogues, were performed on insulin-naïve type 1 diabetic patients. When those two trials were analyzed separately, CSII did not produce any relevant effect on HbA1c (difference from control: - 0.10[- 0.38; + 0.17]%; p = 0.46). No meta-analysis could be performed on either severe hypoglycemia or DKA, which were not reported by one of the two trials. CSII seems to produce a small improvement in HbA1c in patients with type 1 diabetes inadequately controlled with MDI. This apparent effect, which could be partly due to publication bias, is smaller when MDI is properly performed using basal-bolus schemes with short-acting insulin analogues. Other outcomes different from HbA1c (such as quality of life) could be relevant for the choice of CSII instead of MDI. In addition, further studies are needed to better define the profile of patients who could benefit most from CSII.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Cetoacidose Diabética/tratamento farmacológico , Cetoacidose Diabética/epidemiologia , Esquema de Medicação , Combinação de Medicamentos , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Masculino , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
7.
Drugs ; 79(2): 173-186, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30623349

RESUMO

The recent introduction of the second-generation long-acting analogue insulins degludec and insulin glargine U300 have increased the choice of basal insulin therapy for patients with type 2 diabetes. The pharmacokinetic and pharmacodynamic properties of these insulins result in a flatter profile that lasts over 24 h and provides an increased window of administration of 6 h once daily. Large-scale multicentre randomised clinical trial programmes (BEGIN for degludec U100 and U200 and EDITION for glargine U300) evaluating these insulin therapies against glargine U100 have demonstrated that they are either non-inferior or superior for glycaemic efficacy and safety, but less likely to result in severe or nocturnal hypoglycaemia than glargine U100. The disposable pen devices for these insulins have been designed with patient satisfaction and convenience in mind. No concerns have arisen with adverse events with insulin analogues or cardiovascular safety from the ORIGIN and DEVOTE trials. As they demonstrate equivalent glycaemic efficacy to other basal insulins, they should be considered more in selected patient groups including those with recurrent or increased risk of hypoglycaemia, especially severe or nocturnal episodes, in the elderly or those living alone, and in patients with multiple co-morbidities such as cardiovascular or renal disease.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Glicemia , Esquema de Medicação , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Resultado do Tratamento
8.
Pediatr Diabetes ; 20(3): 314-320, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30666772

RESUMO

BACKGROUND: Historically, data on the rate of hyperglycemia and ketosis have not been collected in clinical trials. However, it is clinically important to assess the rate of these events in children with type 1 diabetes (T1D). This question was addressed in two pediatric trials using insulin degludec (degludec). OBJECTIVE: To assess the rate of hyperglycemia and ketosis in two-phase 3b trials investigating degludec (Study 1) and degludec with insulin aspart (IDegAsp [Study 2]) vs insulin detemir (IDet). SUBJECTS: Patients (aged 1-17 years inclusive) with T1D treated with insulin for ≥3 months. METHODS: Study 1: patients were randomized to degludec once daily (OD) or IDet OD/twice daily (BID) for 26 weeks, followed by a 26-week extension phase. Study 2: patients were randomized to IDegAsp OD or IDet OD/BID for 16 weeks. Bolus mealtime IAsp was included in both studies. In Study 1, hyperglycemia was recorded if plasma glucose (PG) was >11.1 mmol/L, with ketone measurement required with significant hyperglycemia (>14.0 mmol/L). In Study 2, hyperglycemia was recorded with PG >14.0 mmol/L where the subject looked/felt ill, with ketone measurement also required in these hyperglycemic patients. In this post hoc analysis, the hyperglycemia threshold was 14.0 mmol/L for uniformity. RESULTS: Despite similar rates of hyperglycemia with degludec/IDegAsp compared with IDet, the rates of ketosis were lower with degludec/IDegAsp. CONCLUSIONS: These trials, the first to systematically collect data on ketosis in pediatric patients with T1D, demonstrate the potential of degludec/IDegAsp to reduce rates of metabolic decompensation, compared with IDet.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/epidemiologia , Hiperglicemia/epidemiologia , Insulina Detemir/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Adolescente , Glicemia/metabolismo , Criança , Pré-Escolar , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Combinação de Medicamentos , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Lactente , Insulina Aspart/administração & dosagem , Insulina Aspart/efeitos adversos , Insulina Detemir/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Masculino , Estudos Retrospectivos
9.
Diabetes Obes Metab ; 21(3): 622-630, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30362250

RESUMO

AIMS: To investigate the association between day-to-day fasting self-monitored blood glucose (SMBG) variability and risk of hypoglycaemia in type 1 (T1D) and type 2 diabetes (T2D), and to compare day-to-day fasting SMBG variability between treatments with insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100). MATERIALS AND METHODS: Data were retrieved from two double-blind, randomized, treat-to-target, two-period (32 weeks each) crossover trials of degludec vs glargine U100 in T1D (SWITCH 1, n = 501) and T2D (SWITCH 2, n = 720). Available fasting SMBGs were used to determine the standard deviation (SD) of day-to-day fasting SMBG variability for each patient and the treatment combination. The association between day-to-day fasting SMBG variability and overall symptomatic, nocturnal symptomatic and severe hypoglycaemia was analysed for the pooled population using linear regression, with fasting SMBG variability included as a three-level factor defined by population tertiles. Finally, day-to-day fasting SMBG variability was compared between treatments. RESULTS: Linear regression showed that day-to-day fasting SMBG variability was significantly associated with overall symptomatic, nocturnal symptomatic and severe hypoglycaemia risk in T1D and T2D (P < 0.05). Day-to-day fasting SMBG variability was significantly associated (P < 0.01) with all categories of hypoglycaemia risk, with the exception of severe hypoglycaemia in T2D when analysed within tertiles. Degludec was associated with 4% lower day-to-day fasting SMBG variability than glargine U100 in T1D (P = 0.0082) and with 10% lower day-to-day fasting SMBG variability in T2D (P < 0.0001). CONCLUSIONS: Higher day-to-day fasting SMBG variability is associated with an increased risk of overall symptomatic, nocturnal symptomatic and severe hypoglycaemia. Degludec has significantly lower day-to-day fasting SMBG variability vs glargine U100.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Jejum/sangue , Hipoglicemia/induzido quimicamente , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Adolescente , Adulto , Glicemia/metabolismo , Automonitorização da Glicemia , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Jejum/fisiologia , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Insulina Glargina/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Diabetes Metab ; 45(4): 330-340, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30496834

RESUMO

AIM: Second-generation basal insulin analogues (e.g. insulin degludec, insulin glargine 300 U/mL), were designed to further extend the duration of insulin action and reduce within-day and day-to-day variability, and consequently hypoglycaemia risk, versus earlier long-acting basal insulins. This review examines the pharmacokinetic/pharmacodynamic characteristics of insulin degludec (100, 200 U/mL) and insulin glargine (100, 300 U/mL), and their influence on clinical outcomes. METHODS: Available pharmacokinetic/pharmacodynamic publications comparing insulin degludec and insulin glargine were reviewed. RESULTS: Both insulin degludec and insulin glargine 300 U/mL have more prolonged and stable pharmacokinetic/pharmacodynamic profiles than the earlier basal insulin analogue, insulin glargine 100 U/mL. Insulin glargine 300 U/mL (0.4 U/kg, morning) showed a more stable pharmacodynamic profile (20% lower within-day variability [P = 0.047]) and more even 24-h distribution (over each 6-h quartile) than insulin degludec 100 U/mL, whereas the supratherapeutic 0.6 U/kg dose demonstrated a similar, albeit non-significant, trend. In contrast, a second clamp study indicated lower day-to-day variability in the 24-h glucose-lowering effect (variance ratio 3.70, P < 0.0001), and more even dosing over each 6-h quartile, with insulin degludec 200 U/mL versus insulin glargine 300 U/mL (0.4 U/kg, evening). Methodological differences and differences in bioequivalence that may explain these discrepancies are discussed. CONCLUSIONS: Compared with earlier insulin analogues, second-generation basal insulins have improved pharmacokinetic/pharmacodynamic profiles that translate into clinical benefits, primarily reduced nocturnal-hypoglycaemia risk. Additional head-to-head comparisons of insulin degludec and insulin glargine 300 U/mL at bioequivalent doses, utilising continuous glucose monitoring and/or real-world evidence, are required to elucidate the differences in their pharmacological and clinical profiles.


Assuntos
Insulina Glargina/administração & dosagem , Insulina Glargina/farmacocinética , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/farmacocinética , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Prognóstico
11.
Diabetes Obes Metab ; 21(2): 349-356, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30221457

RESUMO

AIMS: To compare the time spent in specified glycaemic ranges in people with type 1 diabetes (T1D) during 5 consecutive days of moderate-intensity exercise while on either 100% or 75% of their usual insulin degludec (IDeg) dose. MATERIALS AND METHODS: Nine participants with T1D (four women, mean age 32.1 ± 9.0 years, body mass index 25.5 ± 3.8 kg/m2 , glycated haemoglobin 55 ± 7 mmol/mol (7.2% ± 0.6%) on IDeg were enrolled in the trial. Three days before the first exercise period, participants were randomized to either 100% or 75% of their usual IDeg dose. Participants exercised on a cycle ergometer for 55 minutes at a moderate intensity for 5 consecutive days. After a 4-week wash-out period, participants performed the last exercise period for 5 consecutive days with the alternate IDeg dose. Time spent in specified glycaemic ranges, area under the curve and numbers of hypoglycaemic events were compared for the 5 days on each treatment allocation using a paired Students' t test, Wilcoxon matched-pairs signed-rank test and two-way ANOVA. RESULTS: Time spent in euglycaemia over 5 days was greater for the 75% IDeg dose versus the 100% IDeg dose (4008 ± 938 minutes vs. 3566 ± 856 minutes; P = 0.04). Numbers of hypoglycaemic events (P = 0.91) and time spent in hypoglycaemia (P = 0.07) or hyperglycaemia (P = 0.38) was similar for both dosing schemes. CONCLUSIONS: A 25% reduction in usual IDeg dose around regular exercise led to more time spent in euglycaemia, with small effects on time spent in hypo- and hyperglycaemia.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Exercício/fisiologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Adolescente , Adulto , Idoso , Glicemia/efeitos dos fármacos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
12.
Pediatr Diabetes ; 19(7): 1263-1270, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30014589

RESUMO

BACKGROUND: Insulin degludec/insulin aspart (IDegAsp) is a fixed soluble co-formulation of basal and bolus insulin. OBJECTIVE: To evaluate efficacy and safety of IDegAsp in pediatric patients with type 1 diabetes (T1D). SUBJECTS: Children and adolescents (aged 1 to <18 years) with T1D. METHODS: A 16-week, phase 3b, treat-to-target, parallel-group, open-label, non-inferiority trial was conducted at 63 sites in 14 countries from October 2013 to November 2014. Patients were randomized 1:1 (age stratified: 1-<6 years; 6-<12 years; 12-<18 years) to IDegAsp once daily (OD) plus insulin aspart (IAsp) for remaining meals (IDegAsp + IAsp), or IDet OD or twice daily plus mealtime IAsp (IDet + IAsp). The primary end-point was HbA1c change from baseline at week 16. RESULTS: A total of 362 participants were randomized to IDegAsp + IAsp (n = 182) or IDet + IAsp (n = 180). HbA1c decreased from baseline to week 16 by 0.3% in both groups (estimated treatment difference: -0.04%-points [-0.23; 0.15]95%CI (-0.45 mmol/mol [-2.51; 1.60]95%CI ), confirming non-inferiority. There were no significant differences between treatment groups in fasting or self-measured plasma glucose. Confirmed hypoglycemia rates did not significantly differ between groups. There was a significant reduction in basal and total insulin dose with IDegAsp + IAsp vs IDet + IAsp (post hoc analysis). Mean number of injections/day was 3.6 and 4.9 with IDegAsp + IAsp and IDet + IAsp, respectively (post hoc analysis). A non-significant higher rate of severe hypoglycemia was observed with IDegAsp + IAsp vs IDet + IAsp. The most frequent adverse events in both groups were hypoglycemia, headache, and nasopharyngitis. CONCLUSIONS: IDegAsp + IAsp was non-inferior to IDet + IAsp regarding HbA1c, had similar hypoglycemia rates and required fewer injections.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Adolescente , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Lactente , Insulina de Ação Prolongada/efeitos adversos , Cetose , Masculino
13.
Ann Intern Med ; 169(3): 165-174, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29987326

RESUMO

Background: Basal insulin analogues aim for protracted glycemic control with minimal adverse effects. Purpose: To assess the comparative efficacy and safety of basal insulin analogues for adults with type 2 diabetes mellitus (T2DM). Data Sources: Several databases from inception to April 2018 without language restrictions, ClinicalTrials.gov to April 2018, references of reviews, and meeting abstract books. Study Selection: Randomized trials lasting at least 12 weeks that compared efficacy (change in hemoglobin A1c [HbA1c] level from baseline [primary outcome]; percentage of patients with HbA1c level <7% at end of study and change in body weight [secondary outcomes]) and safety (hypoglycemia) of basal insulin analogues. Data Extraction: Two authors independently extracted data and assessed risk of bias for each outcome. All authors evaluated overall confidence in the evidence. Data Synthesis: Thirty-nine trials (26 195 patients) assessed 10 basal insulin analogues. Low- to very-low-quality evidence indicated that thrice-weekly degludec (Deg-3TW) was inferior to most other regimens for reducing HbA1c level, with mean differences ranging from 0.21% (vs. degludec, 100 U/mL [Deg-100]) to 0.32% (vs. glargine, 300 U/mL [Glar-300]). High- to moderate-quality evidence suggested that detemir had a favorable weight profile versus all comparators, and Glar-300 was associated with less weight gain than glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence suggested that Deg-100, Deg-200, and Glar-300 were associated with lower incidence of nocturnal hypoglycemia than detemir, Glar-100, LY2963016, and neutral protamine lispro (NPL). Incidence of severe hypoglycemia did not differ among regimens, except NPL, which was associated with increased risk versus Deg-100, detemir, Glar-100, and Glar-300. Limitations: Results are based mostly on indirect comparisons. Confidence in summary estimates is low or very low due to individual-study limitations, imprecision, or inconsistency. Conclusion: Low-quality evidence suggests that basal insulin analogues for T2DM do not substantially differ in their glucose-lowering effect. Low- and very-low-quality evidence suggests some regimens may be associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300). Primary Funding Source: None. (PROSPERO: CRD42016037055).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Adulto , Humanos , Hipoglicemiantes/efeitos adversos , Insulina Detemir/efeitos adversos , Insulina Detemir/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/efeitos adversos , Insulina de Ação Prolongada/uso terapêutico , Meta-Análise em Rede , Medição de Risco
14.
Diabetes Obes Metab ; 20(9): 2148-2158, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29938887

RESUMO

AIMS: To compare clinical outcomes in patients with type 2 diabetes (T2D) switching from insulin glargine 100 units/mL (Gla-100) or insulin detemir (IDet) to insulin glargine 300 units/mL (Gla-300) or insulin degludec (IDeg). MATERIALS AND METHODS: We conducted a retrospective, observational study of electronic medical records for Gla-300/IDeg adult switchers (March 1, 2015 to January 31, 2017) with active records for 12-month baseline (glycated haemoglobin [HbA1c] used a 6-month baseline period) and 6-month follow-up periods. Gla-300 and IDeg switchers were propensity score-matched using baseline demographic and clinical characteristics. Outcomes were HbA1c change and goal attainment (among patients with HbA1c captured at follow-up), and hypoglycaemia with fixed follow-up (intention-to-treat [ITT]; 6 months) and variable follow-up (on-treatment [OT]; to discontinuation or 6 months). RESULTS: Each matched cohort comprised 1592 patients. The mean decrease in HbA1c and HbA1c goal (<7.0% [53 mmol/mol] and <8.0% [64 mmol/mol]) attainment rates were similar for Gla-300 (n = 742) and IDeg (n = 727) switchers. Using fixed follow-up (ITT method), hypoglycaemia incidence decreased significantly from baseline with Gla-300 (all hypoglycaemia: 15.6% to 12.7%; P = .006; hypoglycaemia associated with inpatient/emergency department [ED] encounter: 5.3% to 3.5%; P = .007), but not with IDeg. After adjusting for baseline hypoglycaemia, no significant differences in hypoglycaemia incidence and event rate were found at follow-up (ITT) for Gla-300 vs IDeg. Using variable follow-up (OT), hypoglycaemia incidence was similar in both groups, but Gla-300 switchers had a lower inpatient/ED hypoglycaemia event rate at follow-up (adjusted rate ratio 0.56; P = .016). CONCLUSIONS: In a real-world setting, switching from Gla-100 or IDet to Gla-300 or IDeg was associated with similar improvements in glycaemic control and hypoglycaemia in adult patients with T2D.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Substituição de Medicamentos , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Idoso , Glicemia , Pesquisa Comparativa da Efetividade , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobina A Glicada , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/análogos & derivados , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
15.
Diabetes Obes Metab ; 20(10): 2371-2378, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29797389

RESUMO

AIM: To evaluate the cost-effectiveness of IDegLira versus basal-bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK. METHODS: A Microsoft Excel model was used to evaluate the cost-utility of IDegLira versus BBT over a 1-year time horizon. Clinical input data were taken from the treat-to-target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c <7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event-related disutilities were taken from published sources. Extensive sensitivity analyses were performed. RESULTS: IDegLira was associated with an improvement of 0.05 quality-adjusted life years (QALYs) versus BBT, due to reductions in non-severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost-effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses. CONCLUSIONS: IDegLira is a cost-effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/economia , Custos de Medicamentos/estatística & dados numéricos , Insulina Aspart/administração & dosagem , Insulina Glargina/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Liraglutida/administração & dosagem , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Automonitorização da Glicemia/economia , Automonitorização da Glicemia/estatística & dados numéricos , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Insulina Aspart/efeitos adversos , Insulina Aspart/economia , Insulina Glargina/efeitos adversos , Insulina Glargina/economia , Insulina de Ação Prolongada/efeitos adversos , Insulina de Ação Prolongada/economia , Liraglutida/efeitos adversos , Liraglutida/economia , Resultado do Tratamento , Reino Unido/epidemiologia
17.
Diabetes Metab ; 44(5): 402-409, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29548798

RESUMO

AIMS: To explore comparative glycaemic control and hypoglycaemia incidence with insulin degludec 100U/mL (IDeg) or insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in trial-level meta-analyses of phase 3a clinical trials including people with type-2 diabetes. METHODS: Meta-analyses of HbA1c, fasting plasma glucose (FPG), average 24h self-measured plasma glucose (SMPG), pre-breakfast SMPG and hypoglycaemia incidence and rate, using data from the BEGIN (IDeg) and EDITION (Gla-300) insulin development programmes, were performed. RESULTS: In BEGIN, despite greater FPG reduction with IDeg than Gla-100, HbA1c reduction was greater with Gla-100 (mean difference [95% CI] in HbA1c change: 0.09 [0.01-0.18] %) whereas in EDITION, there was no difference in FPG and HbA1c reduction between Gla-300 and Gla-100. Risk of nocturnal confirmed (<3.1mmol/L [<56mg/dL]) or severe hypoglycaemia, but not anytime (24h) events, was lower with IDeg than Gla-100 (relative risk [RR] 0.79 [0.66-0.94]) whereas Gla-300 was associated with reduced risk of nocturnal (RR 0.75 [0.61-0.92]) and anytime (24h) (RR 0.81 [0.69-0.94]) confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia versus Gla-100. CONCLUSIONS: These trial-level meta-analyses suggest that despite greater reductions in FPG, IDeg was associated with less improvement in HbA1c versus Gla-100, with a hypoglycaemia benefit only evident at night. In contrast, Gla-300 showed similar HbA1c reduction to Gla-100, accompanied by lower risk of hypoglycaemia both at night and at any time of day. Gla-300 and IDeg appear more similar than dissimilar, but head-to-head trials are required.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Diabetes Mellitus Tipo 2/sangue , Humanos , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Incidência , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
Curr Med Res Opin ; 34(6): 1117-1124, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29504812

RESUMO

OBJECTIVE: This study assessed training time with the dulaglutide single-use pen (SUP) and the insulin degludec disposable prefilled pen (FlexTouch®) in self-injection-naïve patients with type 2 diabetes mellitus (T2DM) in Japan. METHODS: This multi-center, open-label, comparative, crossover study measured training time with the dulaglutide SUP vs FlexTouch®. Participants learned how to use both devices in a randomly assigned order. Healthcare providers (HCP) conducted the training. The primary end-point was the time required to train self-injection-naïve T2DM participants to self-inject correctly using each device. Secondary end-points included performance measures, such as success and error rates, patient perceptions related to ease-of-use, and factors associated with training time and performance. RESULTS: Overall, 48 participants were randomized and completed the study. The mean training time to achieve correct administration was significantly shorter with the dulaglutide SUP vs FlexTouch® (7.4 min vs 19.7 min, p < .001). The proportions of participants who successfully completed the mock injection without error were similar for both devices. Ninety-two percent (44/48) of participants reported that the dulaglutide SUP was easier to use than FlexTouch®. CONCLUSIONS: In this study, participants required a shorter training time to achieve correct administration with the dulaglutide SUP, and had a higher preference for the dulaglutide SUP, when compared to FlexTouch®. These data suggest that the dulaglutide SUP is easy-to-use, which may decrease the burden on HCPs to train diabetic patients how to administer injection therapy and reduce patient injection hurdles, such as needle fear.


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Fragmentos Fc das Imunoglobulinas , Sistemas de Infusão de Insulina , Insulina de Ação Prolongada , Preferência do Paciente/estatística & dados numéricos , Proteínas Recombinantes de Fusão , Adulto , Idoso , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Injeções/instrumentação , Injeções/métodos , Injeções/psicologia , Sistemas de Infusão de Insulina/psicologia , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Japão , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Autoadministração/métodos , Autoadministração/psicologia
19.
Diabetes Care ; 41(5): 1009-1016, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29483185

RESUMO

OBJECTIVE: In patients with uncontrolled type 2 diabetes on basal insulin, prandial insulin may be initiated. We assessed the efficacy and safety of initiating insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus basal-bolus insulin. RESEARCH DESIGN AND METHODS: A phase 3b trial examined patients with uncontrolled type 2 diabetes on insulin glargine (IGlar U100) 20-50 units/day and metformin, randomized to IDegLira or IGlar U100 and insulin aspart ≤4 times per day. RESULTS: Glycated hemoglobin (HbA1c) decreased from 8.2% (66 mmol/mol) to 6.7% (50 mmol/mol) with IDegLira and from 8.2% (67 mmol/mol) to 6.7% (50 mmol/mol) with basal-bolus (estimated treatment difference [ETD] -0.02% [95% CI -0.16, 0.12]; -0.2 mmol/mol [95% CI -1.7, 1.3]), confirming IDegLira noninferiority versus basal-bolus (P < 0.0001). The number of severe or blood glucose-confirmed symptomatic hypoglycemia events was lower with IDegLira versus basal-bolus (risk ratio 0.39 [95% CI 0.29, 0.51]; rate ratio 0.11 [95% CI 0.08, 0.17]). Body weight decreased with IDegLira and increased with basal-bolus (ETD -3.6 kg [95% CI -4.2, -2.9]). Fasting plasma glucose reductions were similar; lunch, dinner, and bedtime self-monitored plasma glucose measurements were significantly lower with basal-bolus. Sixty-six percent of patients on IDegLira vs. 67.0% on basal-bolus achieved HbA1c <7.0% (53 mmol/mol). Total daily insulin dose was lower with IDegLira (40 units) than basal-bolus (84 units total; 52 units basal). CONCLUSIONS: In patients with uncontrolled type 2 diabetes on IGlar U100 and metformin, IDegLira treatment elicited HbA1c reductions comparable to basal-bolus, with statistically superior lower hypoglycemia rates and weight loss versus weight gain.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Insulina/administração & dosagem , Liraglutida/administração & dosagem , Liraglutida/efeitos adversos , Metformina/administração & dosagem , Adulto , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/análise , Humanos , Insulina/efeitos adversos , Insulina Aspart/administração & dosagem , Insulina Aspart/efeitos adversos , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Diabetes Obes Metab ; 20(7): 1585-1592, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29451706

RESUMO

AIMS: To investigate whether the proven benefits of insulin degludec (IDeg) combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes. MATERIALS AND METHODS: This was a post hoc pooled analysis of 5 phase III randomized, 26-week, open-label, treat-to-target trials comparing IDegAsp twice daily (n = 1111) with one of two comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) categories, as well as by baseline duration of diabetes or body mass index (BMI) categories. RESULTS: We conducted a meta-analysis of 5 clinical trials: NCT01513590, NCT01009580, NCT01059812, NCT01680341 and NCT01713530. End-of-trial results were broadly consistent, with differences between IDegAsp and comparators observed in phase III trials. HbA1c results were similar for IDegAsp and the comparators in all baseline characteristic (HbA1c, duration of diabetes or BMI) and category groups (number ranges). Significantly lower FPG level was observed with IDegAsp vs comparators in all baseline characteristic and most category groups (excluding FPG <5.5 mmol/L). Significantly lower insulin doses were observed with IDegAsp vs comparators in all baseline characteristic and half of the category groups, and significantly lower rates of confirmed and nocturnal confirmed hypoglycaemia were observed with IDegAsp vs comparators in all baseline variable and category groups. CONCLUSIONS: IDegAsp retains a consistent safety and efficacy profile in patients with different baseline characteristics.


Assuntos
Atividades Cotidianas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Glicemia/análise , Índice de Massa Corporal , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Progressão da Doença , Esquema de Medicação , Combinação de Medicamentos , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Obesidade/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto
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