Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Insulina de Ação Prolongada , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Insulina de Ação Prolongada/uso terapêutico , Insulina de Ação Prolongada/efeitos adversos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resultado do Tratamento , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológicoRESUMO
AIM: To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves ß-cell responsivity in healthy men. METHODS: In a double-blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non-insulin-treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.36 years; body mass index, 27.77 ± 0.66 kg/m2; HbA1c, 6.86% ± 0.08%; Homeostatic Model Assessment of Insulin Resistance (HOMA-IR, 3.44 ± 0.39) 60 minutes before an oral glucose tolerance test (oGTT). Key outcomes were compared with previous results in men with normal weight or obesity. RESULTS: Oxytocin compared with placebo increased plasma oxytocin concentrations and reduced the heart rate, but did not alter glucose metabolism in the 3 hours after oGTT onset (area under the curve, glucose, 2240 ± 80.5 vs. 2190 ± 69.5 mmol/L × min; insulin, 45 663 ± 4538 vs. 44 343 ± 4269 pmol/L × min; C-peptide, 235 ± 5.1 vs. 231 ± 15.9 nmol/L × min). CONCLUSIONS: This outcome contrasts with the oxytocin-induced attenuation of early postprandial glucose excursions in normal-weight individuals, but is in line with the absence of respective effects in men with obesity. We conclude that insulin resistance in type 2 diabetes is associated with decreased sensitivity to the acute glucoregulatory effect of oxytocin in male individuals.
Assuntos
Glicemia , Estudos Cross-Over , Diabetes Mellitus Tipo 2 , Teste de Tolerância a Glucose , Resistência à Insulina , Ocitocina , Humanos , Masculino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Ocitocina/administração & dosagem , Ocitocina/sangue , Pessoa de Meia-Idade , Método Duplo-Cego , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Insulina/sangue , Administração Intranasal , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/sangue , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/efeitos dos fármacosAssuntos
Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Satisfação do Paciente , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hipoglicemiantes/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Japão/epidemiologia , Comportamento Alimentar , Idoso , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/efeitos dos fármacos , Resultado do Tratamento , População do Leste AsiáticoRESUMO
AIM: To compare the effectiveness of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with adding basal insulin among adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) already treated with a sodium-glucose co-transporter-2 inhibitor (SGLT2i) and not reaching their glycaemic control targets. METHODS: A retrospective analysis of the Canadian LMC Diabetes Registry was conducted. Adults who initiated a GLP-1 RA were matched 1:1 to adults who initiated basal insulin in a T2D and CKD population. Changes in metabolic outcomes were evaluated at 26-52 weeks following the therapy start date. RESULTS: Propensity score matching was used to match participants who initiated a GLP-1 RA to participants who initiated basal insulin (n = 153/cohort). A significantly greater reduction in HbA1c at 26-52 weeks of follow-up was observed in the GLP-1 RA cohort compared with the basal insulin cohort (-1.3% ± 1.4% vs. -1.1% ± 1.4%, P = .03). Weight was significantly reduced (-3.4 ± 3.7 vs. 2.6 ± 4.5 kg, P < .001), and the estimated glomerular filtration rate decline slowed significantly (-0.3 ± 8.2 vs. -2.4 ± 10.4 mL/min/1.73m2, P = .02), but the change in albuminuria was not significantly different (-5.7 ± 38.1 vs. -0.5 ± 38.3 mg/mmol, P = .47) at follow-up in the GLP-1 RA group compared with the basal insulin group. No differences in self-reported hypoglycaemic events per week and therapy discontinuations were reported between the cohorts. CONCLUSIONS: The study shows the real-world effectiveness of GLP-1 RA therapy for T2D and CKD. GLP-1 RAs provided superior reductions in HbA1c and weight, and greater kidney protection, compared with basal insulin among adults with T2D and CKD already treated with an SGLT2i.
Assuntos
Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hemoglobinas Glicadas , Hipoglicemiantes , Insulina , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Hipoglicemiantes/uso terapêutico , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/efeitos dos fármacos , Insulina/uso terapêutico , Canadá/epidemiologia , Controle Glicêmico/métodos , Nefropatias Diabéticas/tratamento farmacológico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Sistema de Registros , Resultado do Tratamento , Taxa de Filtração Glomerular/efeitos dos fármacosRESUMO
AIM: To study safety, efficacy and weight loss with ADO09, a co-formulation of insulin A21G and pramlintide, in type 1 diabetes. MATERIALS AND METHODS: A randomized, two-arm ambulatory 16-week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment. RESULTS: A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed. CONCLUSIONS: These results extend previous observations on the efficacy and safety of this insulin/pramlintide co-formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia.
Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Hemoglobinas Glicadas , Hipoglicemiantes , Insulina Lispro , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Redução de Peso , Humanos , Insulina Lispro/uso terapêutico , Insulina Lispro/administração & dosagem , Polipeptídeo Amiloide das Ilhotas Pancreáticas/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Masculino , Feminino , Hipoglicemiantes/uso terapêutico , Adulto , Redução de Peso/efeitos dos fármacos , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Pessoa de Meia-Idade , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Insulina/análogos & derivados , Insulina/uso terapêutico , Insulina/administração & dosagem , Combinação de Medicamentos , Resultado do Tratamento , Hipoglicemia/induzido quimicamenteRESUMO
To investigate the safety and efficacy of long-acting glucagon like peptide-1 receptor agonists in overweight or obese patients with type 2 diabetes. Overweight or obese patients with type 2 diabetes from July 2021 to June 2022 were randomly divided into control group (metformin) and experimental group (metformin + dulaglitide or semaglutide). Repeated measures analysis of variance was used to compare Hemoglobin A1c, fasting plasma glucose and body mass index (BMI) of patients before treatment, 6 months and 12 months after treatment. The adverse reactions of patients before treatment and 12 months after treatment were analyzed. The time effect of Hemoglobin A1c, fasting plasma glucose and BMI in the control group (nâ =â 35) and the experimental group (nâ =â 32) were statistically significant (Pâ <â .001), and the intergroup effect of BMI was statistically significant (Pâ <â .05). The interaction effect of BMI was statistically significant (Pâ <â .001). The BMI level of the experimental group was lower than that of the control group at 6 and 12 months after treatment (Pâ <â .001). There was no significant difference in the incidence of adverse reactions between the 2 groups (Pâ >â .05). Long-acting glucagon like peptide-1 receptor agonists, such as dulaglitide and semaglutide, not only reduce glycosylated hemoglobin levels, but also significantly improve BMI in overweight or obese patients with type 2 diabetes.
Assuntos
Glicemia , Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon , Hemoglobinas Glicadas , Hipoglicemiantes , Metformina , Obesidade , Sobrepeso , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Masculino , Pessoa de Meia-Idade , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/análise , Obesidade/tratamento farmacológico , Obesidade/complicações , Metformina/uso terapêutico , Sobrepeso/tratamento farmacológico , Sobrepeso/complicações , Glicemia/efeitos dos fármacos , Glicemia/análise , Idoso , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Análise de Variância , Adulto , Quimioterapia Combinada , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Proteínas Recombinantes de FusãoRESUMO
AIM: Recently, the development of the oral glucagon-like peptide-1 receptor agonist semaglutide has drawn a great deal of attention. This study aimed to compare the effectiveness of oral glucagon-like peptide-1 receptor agonist semaglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors on glycaemic control and several metabolic parameters in patients with type 2 diabetes mellitus over a 6-month period. METHODS: Fifty-nine participants were included, and we compared various clinical parameters between before and after switching from DPP-4 inhibitors to oral semaglutide in 'study 1' (pre-post comparison) and set the control group using the propensity score matching method in 'study 2'. RESULTS: In 'study 1', 6 months after the switching, the glycated haemoglobin value was significantly reduced from 7.5% to 7.0%, and the body mass index was also decreased from 29.7 kg/m2 to 28.8 kg/m2. Such effects were more clearly observed in participants whose glycaemic control was poor. In 'study 2', after 1:1 propensity score matching, 51 participants from each group were matched, and glycaemic control as well as body weight management were improved in the switching group compared with the DPP-4 inhibitor continuation group over the 6-month observation period. CONCLUSION: In this study, including obese participants with poor glycaemic control, switching DPP-4 inhibitors to oral semaglutide showed more beneficial effects on both glycaemic and weight control, irrespective of age, body weight and diabetes duration. Therefore, we should bear in mind that it would be better to start using an oral semaglutide in clinical practice, particularly in obese participants with poor glycaemic control with DPP-4 inhibitors.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon , Hemoglobinas Glicadas , Hipoglicemiantes , Pontuação de Propensão , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Pessoa de Meia-Idade , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Estudos Prospectivos , Idoso , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Japão , Substituição de Medicamentos , Resultado do Tratamento , Glicemia/efeitos dos fármacos , Controle Glicêmico/métodos , Administração Oral , População do Leste AsiáticoRESUMO
AIM: To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) in people with suboptimally controlled type 2 diabetes (T2D) in China. METHODS: INITIATION (NCT05002933) was a prospective, interventional, multicentre, single-arm, phase IV study conducted in China. Individuals with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin (insulin experienced) were included. The primary endpoint was the change in HbA1c from baseline to week 24. Safety assessments included hypoglycaemia and adverse events (AEs). RESULTS: In total, 568 participants were enrolled and 562 initiated Gla-300 treatment (189 in the insulin-naïve subgroup; 373 in the insulin-experienced subgroup). At week 24, the mean ± standard error (SE) change in HbA1c from baseline was -0.91% ± 0.05% (-9.9 ± 0.5 mmol/mol; P < .0001). Significant HbA1c reductions were also observed in the insulin-naïve (mean ± SE change: -1.38% ± 0.09% [-15.1 ± 1.0 mmol/mol]) and insulin-experienced (-0.68% ± 0.05% [-7.4 ± 0.5 mmol/mol]) subgroups (both P < .0001). During the 24-week treatment period, the incidence of confirmed hypoglycaemia (plasma glucose ≤ 3.9 mmol/L) was 39.7% for all hypoglycaemia and 13.3% for nocturnal hypoglycaemia; the incidence of severe hypoglycaemia was low (0.5%). Overall, treatment-emergent AEs (TEAEs) were reported in 126 participants (22.4%), with no serious treatment-related TEAEs. CONCLUSIONS: Gla-300 was effective in improving glycaemic control and had a relatively low risk of hypoglycaemia in people with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin in China.
Assuntos
Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Hipoglicemia , Hipoglicemiantes , Insulina Glargina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Insulina Glargina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Feminino , China/epidemiologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/administração & dosagem , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Estudos Prospectivos , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Resultado do Tratamento , Adulto , Controle Glicêmico/efeitos adversosRESUMO
BACKGROUND: No comprehensive meta-analysis has examined and consolidated the effectiveness and safety of anagliptin in treating type 2 diabetes mellitus (T2D). To bridge this knowledge gap, we undertook this meta-analysis. METHODS: Randomized controlled trials involving patients with T2D receiving anagliptin were sought after through electronic databases. The control arm consisted of either an active comparator (active control group [ACG]) or a placebo (passive control group [PCG]). The primary outcome was glycated hemoglobin (HbA1c), with secondary outcomes including fasting plasma glucose (FPG) and lipid profiles and adverse events. RESULTS: From the 226 articles first examined, 10 randomized controlled trials with 970 participants were analyzed. Reductions in HbA1c (mean difference [MD]: -0.03%, 95% confidence interval [CI]: -0.14 to 0.14, Pâ =â .51, I2 = 9%) and FPG (MD: 0.03 mmol/L, 95% CI: -0.30 to 0.35, Pâ =â .87, I2 = 42%) were similar in the anagliptin group and ACG. Anagliptin reduced FPG better than placebo (MD: -1.25 mmol/L, 95% CI: -1.87 to -0.64, Pâ <â .0001, I2 = 0%). Sufficient data were unavailable to analyze the HbA1c lowering with anagliptin versus placebo. Among the lipid parameters, changes in total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B48, and apolipoprotein B100 were identical between the anagliptin and control groups (PCG and ACG). Anagliptin was better than ACG at lowering low-density lipoprotein cholesterol but not as good at lowering triglyceride. Adverse events were infrequent and similar in the anagliptin and control groups (PCG and ACG). CONCLUSION: Anagliptin positively affects glucose control and is safe for managing T2D. Its low-density lipoprotein cholesterol-lowering effect warrants further investigation.
Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Hemoglobinas Glicadas , Pirimidinas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Humanos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Pirimidinas/uso terapêutico , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/análise , Glicemia/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Lipídeos/sangueRESUMO
AIM: To perform a participant-level post hoc meta-analysis of Phase 3a trials in type 2 diabetes (T2D) to characterize the hypoglycaemia safety and glycaemic efficacy of once-weekly insulin icodec (icodec). MATERIALS AND METHODS: All ONWARDS 1-5 randomized participants were pooled as overall T2D, insulin-naive, an insulin-experienced subgroups, and by once-daily trial comparator (degludec or glargine U100). The main outcomes included incidence and rates of clinically significant and severe hypoglycaemia. Additional endpoints included change in glycated haemoglobin (HbA1c) from baseline and HbA1c target achievement without clinically significant or severe hypoglycaemia. RESULTS: The meta-analysis comprised 3765 participants (1882 icodec vs. 1883 comparators). In the overall T2D pool, clinically significant hypoglycaemia incidence was similar in the icodec group versus the comparator group (17.9% vs. 16.2%, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.94, 1.38); however, rates were low but significantly higher in the icodec group (1.15 vs. 1.00 episodes/participant-year of exposure, estimated rate ratio 1.51 [95% CI 1.24, 1.85]). Fewer severe hypoglycaemic episodes occurred with icodec than with comparators (8 vs. 18). A greater reduction in HbA1c occurred with icodec versus comparators, irrespective of subgroup (estimated treatment difference range [-0.10 to -0.29%]; all p < 0.05). Across subgroups, except for the insulin-experienced subgroup, the odds of achieving HbA1c <53 mmol/mol (7.0%) without clinically significant or severe hypoglycaemia were greater with icodec than with comparators (OR range 1.30-1.55; all p < 0.05). CONCLUSIONS: Icodec was associated with a similar incidence but higher rates of clinically significant hypoglycaemia (equating to one additional hypoglycaemic episode every 6 years) and fewer severe hypoglycaemic episodes versus comparators. Our findings also confirmed the greater efficacy of icodec that was demonstrated in the ONWARDS trial programme.
Assuntos
Diabetes Mellitus Tipo 2 , Esquema de Medicação , Hemoglobinas Glicadas , Hipoglicemia , Hipoglicemiantes , Insulina Glargina , Insulina de Ação Prolongada , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/uso terapêutico , Insulina Glargina/administração & dosagem , Insulina Glargina/uso terapêutico , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Feminino , Ensaios Clínicos Controlados Aleatórios como Assunto , Glicemia/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Fase III como Assunto , Resultado do Tratamento , IncidênciaRESUMO
AIM: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin. MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24. RESULTS: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection. CONCLUSIONS: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone.
Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Glucosídeos , Hemoglobinas Glicadas , Hipoglicemiantes , Metformina , Piperidonas , Pirimidinas , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Metformina/uso terapêutico , Metformina/administração & dosagem , Compostos Benzidrílicos/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Idoso , Piperidonas/uso terapêutico , Piperidonas/administração & dosagem , Piperidonas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/análise , Glicemia/metabolismo , Controle Glicêmico/métodos , Adulto , Resultado do Tratamento , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
Objective: The aim of this meta-analysis was to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in adolescents with overweight/obesity and/or type 2 diabetes mellitus (T2DM) aged <18 years. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched for all randomized controlled trials (RCTs) up to August 2023 comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1,262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, p<0.001) than the control group. However, there was no difference in fasting plasma glucose [fasting plasma glucose (FPG); RD=-2.07 mg/dL, p=0.065] between the two groups. Nonetheless, the experimental group that received exenatide showed no significant reduction in HbA1c (p=0.253) and FPG (p=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28 kg, p=0.002) and body mass index (BMI) (RD=-1.63 kg/m2, p=0.002) compared to the control group. The experimental group was given liraglutide (RD=-2.31 kg, p=0.038) or exenatide (RD=-2.70 kg, p<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. However, for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81 kg/m2, p=0.260). For the experimental group using exenatide, BMI declined more significantly in the intervention group than in the control group (RD=-1.14 kg/m2, p<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide was better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide was more effective than liraglutide.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Sobrepeso , Obesidade Infantil , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Adolescente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Sobrepeso/tratamento farmacológico , Obesidade Infantil/tratamento farmacológico , Glicemia/efeitos dos fármacos , Exenatida/uso terapêutico , Exenatida/administração & dosagem , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Liraglutida/uso terapêutico , Resultado do Tratamento , Obesidade/tratamento farmacológico , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
Type 2 diabetes mellitus (T2DM) is associated with obesity and, therefore, it is important to target both overweight and hyperglycaemia. Glucagon plays important roles in glucose, amino acid and fat metabolism and may also regulate appetite and energy expenditure. These physiological properties are currently being exploited therapeutically in several compounds, most often in combination with glucagon-like peptide-1 (GLP-1) agonism in the form of dual agonists. With this combination, increases in hepatic glucose production and hyperglycaemia, which would be counterproductive, are largely avoided. In multiple randomized trials, the co-agonists have been demonstrated to lead to significant weight loss and, in participants with T2DM, even improved glycated haemoglobin (HbA1c) levels. In addition, significant reductions in hepatic fat content have been observed. Here, we review and discuss the studies so far available. Twenty-six randomized trials of seven different GLP-1 receptor (GLP-1R)/glucagon receptor (GCGR) co-agonists were identified and reviewed. GLP-1R/GCGR co-agonists generally provided significant weight loss, reductions in hepatic fat content, improved lipid profiles, insulin secretion and sensitivity, and in some cases, improved HbA1c levels. A higher incidence of adverse effects was present with GLP-1R/GCGR co-agonist treatment than with GLP-1 agonist monotherapy or placebo. Possible additional risks associated with glucagon agonism are also discussed. A delicate balance between GLP-1 and glucagon agonism seems to be of particular importance. Further studies exploring the optimal ratio of GLP-1 and glucagon receptor activation and dosage and titration regimens are needed to ensure a sufficient safety profile while providing clinical benefits.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Glucagon , Hipoglicemiantes , Obesidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Glucagon/metabolismo , Glucagon/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Receptores de Glucagon/agonistas , Redução de Peso/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , MasculinoRESUMO
AIM: To compare the effectiveness of different basal insulins (BI) prescribed as an add-on to or switch from glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy. MATERIALS AND METHODS: Retrospective, real-world data from electronic medical records of 32 Italian diabetes clinics were used, after propensity score adjustment, to compare effectiveness after 6 months of treatment with second- versus first-generation BI (2BI vs. 1BI) or glargine 300 U/ml versus degludec 100 U/ml (Gla-300 vs. Deg-100), when added to (ADD-ON) or in substitution of (SWITCH) GLP-1 RA. Only comparisons, including a minimum of 100 patients per group, were performed to ensure adequate robustness of the analyses. RESULTS: In the ADD-ON cohort (N = 700), greater benefits of 2BI versus 1BI were found in glycated haemoglobin {HbA1c; estimated mean difference: -0.32% [95% confidence interval (CI) -0.62; -0.02]; p = .04} and fasting blood glucose [FBG; -20.73 mg/dl (95% CI -35.62; -5.84); p = .007]. In the SWITCH cohort (N = 2097), greater benefits of 2BI versus 1BI were found in HbA1c [-0.22% (95% CI -0.42; -0.02); p = .03], FBG [-10.15 mg/dl (95% CI -19.04; -1.26); p = .03], and body weight [-0.67 kg (95% CI -1.30; -0.04); p = .04]. In the SWITCH cohort starting 2BI (N = 688), marked differences in favour of Gla-300 versus Deg-100 were documented in HbA1c [-0.89% (95% CI -1.26; -0.52); p < .001] and FBG [-17.89 mg/dl (95% CI -32.45; -3.33); p = .02]. Using propensity score matching as a sensitivity analysis, the benefit on HbA1c was confirmed [-0.55% (95% CI -1.02; -0.08); p = .02]. BI titration was suboptimal in all examined cohorts. CONCLUSIONS: 2BI are a valuable option to intensify GLP-1 RA therapy. Switching to Gla-300 versus Deg-100 was associated with greater HbA1c improvement.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hemoglobinas Glicadas , Hipoglicemiantes , Insulina Glargina , Insulina de Ação Prolongada , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Feminino , Masculino , Estudos Retrospectivos , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Idoso , Insulina Glargina/uso terapêutico , Insulina Glargina/administração & dosagem , Insulina de Ação Prolongada/uso terapêutico , Glicemia/efeitos dos fármacos , Quimioterapia Combinada , Itália/epidemiologia , Resultado do Tratamento , Pesquisa Comparativa da Efetividade , Substituição de Medicamentos , Hipoglicemia/induzido quimicamente , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
AIM: To compare the efficacy and safety of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs). METHODS: In Soli-D, a 24-week, multicentre, open-label, study, insulin-naïve adults were randomized 1:1 to once-daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium-glucose co-transporter-2 inhibitors. The primary endpoint was non-inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed. RESULTS: At week 24, iGlarLixi showed non-inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: -0.20 [95% confidence interval {CI}: -0.33, -0.07]; P < .001 for non-inferiority; [97.5% CI: -0.35, -0.05]; P = .003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of -1.49 kg in favour of iGlarLixi (97.5% CI: -2.32, -0.66; P < .001). Event rates (per person-year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported. CONCLUSIONS: In Chinese people with T2D suboptimally controlled with OADs, once-daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp.
Assuntos
Diabetes Mellitus Tipo 2 , Combinação de Medicamentos , Hemoglobinas Glicadas , Hipoglicemiantes , Insulina Glargina , Insulina de Ação Prolongada , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/efeitos dos fármacos , Idoso , China/epidemiologia , Insulina Glargina/administração & dosagem , Insulina Glargina/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/uso terapêutico , Insulina de Ação Prolongada/efeitos adversos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Peptídeos/uso terapêutico , Resultado do Tratamento , Adulto , Glicemia/efeitos dos fármacos , Povo Asiático , Administração Oral , Metformina/uso terapêutico , Metformina/administração & dosagem , Metformina/efeitos adversos , Quimioterapia Combinada , Receptor do Peptídeo Semelhante ao Glucagon 2 , População do Leste AsiáticoRESUMO
AIM: To compare the efficacy and safety profiles of recent innovations in type 2 diabetes mellitus (T2DM), which include once-weekly formulations such as tirzepatide, a dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonist, and once-weekly insulin options such as icodec and basal insulin Fc. METHODS: A systematic search of the PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The network meta-analysis protocol was registered at OSF registries (https://osf.io/gd67x). The primary outcome of interest was change in glycated haemoglobin (HbA1c), with change in fasting plasma glucose (FPG), body weight, incidence of hypoglycaemia, and treatment discontinuation as secondary outcomes. RESULTS: Tirzepatide exhibited superior efficacy in reducing HbA1c levels compared with insulin therapies, with the 15-mg dose showing the most significant reduction (mean difference [MD] -1.27, 95% confidence interval [CI] -1.49; -1.0). In terms of FPG reduction, tirzepatide 15 mg ranked highest (MD -0.70, 95% CI -1.05; -0.34), followed by tirzepatide 10 mg and 5 mg. Additionally, tirzepatide led to substantial weight loss, with the 15-mg dose exhibiting the most pronounced effect (MD -12.13, 95% CI -13.98; -10.27). However, a higher incidence of adverse events (AEs) and treatment discontinuation were associated with tirzepatide, particularly at higher doses. CONCLUSION: Tirzepatide, particularly at higher doses, demonstrates superior efficacy in lowering HbA1c and reducing hypoglycaemia risk compared with weekly insulin. However, its use is also associated with a higher incidence of AEs and treatment discontinuation.
Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Hipoglicemiantes , Insulina , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/uso terapêutico , Insulina/efeitos adversos , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Resultado do Tratamento , Glicemia/efeitos dos fármacos , Esquema de Medicação , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Receptor do Peptídeo Semelhante ao Glucagon 2 , Polipeptídeo Inibidor GástricoRESUMO
BACKGROUND: No meta-analysis has holistically analyzed and summarized the therapeutic efficacy and safety of albiglutide in type 2 diabetes (T2D). This meta-analysis addresses this knowledge gap. METHODS: Randomized controlled trials involving patients with T2D receiving albiglutide in the intervention arm and either a placebo or an active comparator in the control arm were searched through electronic databases. The primary outcome was the change from baseline (CFB) in glycated hemoglobin (HbA1c); secondary outcomes included CFB in fasting plasma glucose, body weight, and adverse events (AE). RESULTS: From 443 initially screened articles, data from 12 randomized controlled trials involving 6423 subjects were analyzed. Albiglutide, at both doses, outperformed placebo in terms of HbA1c reductions (for albiglutide 30 mg: mean differences -1.04%, 95% confidence interval [CI] [-1.37--0.72], Pâ <â .00001, I2â =â 89%; and for albiglutide 50 mg: mean differences -1.10%, 95% CI [-1.45--0.75], Pâ <â .00001, I2â =â 90%). Higher proportions of subjects achieved HbA1câ <â 7% in the albiglutide arm than in placebo (for albiglutide 30 mg: odds ratio 6.26, 95% CI [2.50-15.70], Pâ <â .0001, I2â =â 82%; and for albiglutide 50 mg: odds ratio 5.57, 95% CI [2.25-13.80], Pâ =â .0002, I2â =â 84%). Albiglutide had glycemic efficacy comparable to other glucose-lowering drugs. CFB in body weight was similar with albiglutide and placebo. AE profile, including gastrointestinal AE, was identical with albiglutide and placebo, except for higher drug-related AE and injection-site reaction with albiglutide. CONCLUSION: Albiglutide provides reassuring data on good glycemic efficacy, tolerability, and safety over an extended period of clinical use in patients with T2D. Albiglutide 30 mg has comparable efficacy and safety profiles to albiglutide 50 mg.
Assuntos
Diabetes Mellitus Tipo 2 , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Resultado do TratamentoRESUMO
Objectives: This study aimed to evaluate the safety and efficacy of remogliflozin compared to vildagliptin as an add-on drug to metformin in type 2 diabetes mellitus (T2DM) treatment. Metformin is considered a first-line drug in T2DM. However, as the disease progresses with heightened insulin resistance and declining ß-cell function, the use of metformin alone is often inadequate to achieve optimum glucose levels. Methods: This prospective, randomised study was conducted at Maulana Azad Medical College and Associated Hospital in New Delhi, India, between February 2020 to January 2021. This study recruited 60 T2DM patients aged 35-70 years with glycated haemoglobin (HbA1c) >6.5% taking metformin at a daily dosage of 1,500-3,000 mg for ≥3 months. Patients were randomly assigned in a 1:1 ratio to receive either vildagliptin (50 mg) or remogliflozin (100 mg) twice daily for 90 days. The primary endpoint was a change in HbA1c levels from baseline to the end of 90 days whereas secondary endpoints were changes in lipid profile and weight. Results: The decrement in mean HbA1c levels was significantly higher in the remogliflozin group than in the vildagliptin group (-8.1% versus -2.4%; P <0.001). In addition, more significant weight loss was found in remogliflozin-treated patients (-5.2% versus -0.6%; P <0.01). Both treatments were well tolerated throughout the study. Conclusion: Compared to vildagliptin, remoglilflozin was significantly more effective in glycaemic control and weight loss in patients with T2DM and can therefore be considered as an add-on drug in T2DM not adequately controlled by metformin monotherapy.
Assuntos
Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Hipoglicemiantes , Metformina , Vildagliptina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Vildagliptina/farmacologia , Vildagliptina/uso terapêutico , Metformina/uso terapêutico , Metformina/farmacologia , Pessoa de Meia-Idade , Masculino , Feminino , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Estudos Prospectivos , Idoso , Adulto , Quimioterapia Combinada/métodos , Índia , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Glucosídeos/uso terapêutico , Glucosídeos/farmacologia , Resultado do Tratamento , Glicemia/análise , Glicemia/efeitos dos fármacos , Sorbitol/análogos & derivados , Sorbitol/uso terapêutico , Sorbitol/farmacologia , Sorbitol/efeitos adversos , Sorbitol/administração & dosagem , PirazóisRESUMO
To investigate changes in skeletal muscle mass and fat fraction in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) undergoing treatment with Semaglutide for 6months. This single-arm pilot study included 21 patients with MASLD who received semaglutide for T2DM. Body weight, metabolic parameters, liver enzymes, fibrosis markers, skeletal muscle index (cm2/m2), and fat fraction (%) at the L3 level using the two-point Dixon method on magnetic resonance imaging (MRI), as well as liver steatosis and liver stiffness assessed using MRI-based proton density fat fraction (MRI-PDFF) and MR elastography, respectively, were prospectively examined before and 6 months after semaglutide administration. The mean age of the patients was 53 years and 47.6% were females. The median liver steatosis-fraction (%) and skeletal muscle steatosis-fraction values (%) significantly decreased (22.0 vs 12.0; Pâ =â .0014) and (12.8 vs 9.9; Pâ =â .0416) at baseline and 6 months, respectively, while maintaining muscle mass during treatment. Semaglutide also dramatically reduced hemoglobin A1c (%) (6.8 vs 5.8, Pâ =â .0003), AST (IU/L) (54 vs 26, Pâ <â .0001), ALT (IU/L) (80 vs 34, Pâ =â .0004), and γ-GTP (IU/L) levels (64 vs 34, Pâ =â .0007). Although not statistically significant, Body weight (kg) (79.9 vs 77.4), body mass index (BMI) (kg/m2) (28.9 vs 27.6), and liver stiffness (kPa) (28.9 vs 27.6) showed a decreasing trend. Fibrosis markers such as M2BPGi, type IV collagen, and skeletal muscle area did not differ. Semaglutide demonstrated favorable effects on liver and skeletal muscle steatosis, promoting improved liver function and diabetic status.