Metformin and second- or third-generation sulphonylurea combination therapy for adults with type 2 diabetes mellitus.
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ABSTRACT:
SUBMITTER: Madsen KS
PROVIDER: S-EPMC6472662 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In gestational diabetes mellitus (GDM), women are unable to compensate for the increased insulin resistance during pregnancy. Data are limited regarding the pharmacodynamic effects of metformin and glyburide during pregnancy. This study characterized insulin sensitivity (SI), β-cell responsivity, and disposition index (DI) in women with GDM utilizing a mixed-meal tolerance test (MMTT) before and during treatment with glyburide monotherapy (GLY, n = 38), metformin monotherapy (MET, n = 34), or GLY and MET combination therapy (COMBO; n = 36). GLY significantly decreased dynamic β-cell responsivity (31%). MET and COMBO significantly increased SI (121% and 83%, respectively). Whereas GLY, MET, and COMBO improved DI, metformin (MET and COMBO) demonstrated a larger increase in DI (P = 0.05) and a larger decrease in MMTT peak glucose concentrations (P = 0.03) than subjects taking only GLY. Maximizing SI with MET followed by increasing β-cell responsivity with GLY or supplementing with insulin might be a more optimal strategy for GDM management than monotherapy.
| S-EPMC7561209 | biostudies-literature
Project description:For patients with type 2 diabetes mellitus, management of hyperglycemia is typically complex, and few patients successfully achieve and maintain recommended targets for glycated hemoglobin (HbA1c). Increasingly, combination therapy is recommended early in the disease course, or even directly at diagnosis in patients with relatively high HbA1c levels. A recent randomized, placebo-controlled, Phase III trial investigated the initial combination of linagliptin and metformin in patients with inadequate glycemic control to assess the benefits of initial combination compared with monotherapy. Linagliptin and metformin act in complementary ways, and the combination treatment showed superior efficacy compared with either monotherapy. Notably, responses were largest in patients with higher baseline HbA1c levels compared with moderate levels, suggesting this combination could be considered in these patients. This may be particularly relevant for those unwilling to start insulin because they prefer oral therapy or need to avoid body weight gain. Neither metformin nor linagliptin is associated with weight gain, and in this trial the combination was also weight neutral. As this combination therapy was well tolerated, with a low frequency of hypoglycemia, these findings suggest that initial combination of linagliptin plus metformin may have advantages for a large proportion of patients in clinical practice.
| S-EPMC3884752 | biostudies-literature
Project description: Not available
| S-EPMC7386876 | biostudies-literature
Project description:BackgroundMetformin is widely accepted as first-line pharmacotherapy for patients with type 2 diabetes mellitus when glycemic control cannot be achieved by lifestyle interventions alone. However, uncertainty exists regarding the optimal second-line therapy for patients whose diabetes is inadequately controlled by metformin monotherapy. Increased use of newer, more costly agents, along with the rising incidence of type 2 diabetes, carries significant budgetary implications for health care systems. We conducted this analysis to determine the relative costs, benefits and cost-effectiveness of options for second-line treatment of type 2 diabetes.MethodsWe used the United Kingdom Prospective Diabetes Study Outcomes Model to forecast diabetes-related complications, quality-adjusted life-years and costs of alternative second-line therapies available in Canada for adults with type 2 diabetes inadequately controlled by metformin. We obtained clinical data from a systematic review and mixed treatment comparison meta-analysis, and we obtained information on costs and utilities from published sources. We performed extensive sensitivity analyses to test the robustness of results to variation in inputs and assumptions.ResultsSulphonylureas, when added to metformin, were associated with the most favourable cost-effectiveness estimate, with an incremental cost of $12 757 per quality-adjusted life-year gained, relative to continued metformin monotherapy. Treatment with other agents, including thiazolidinediones and dipeptidyl peptidase-4 inhibitors, had unfavourable cost-effectiveness estimates compared with sulphonylureas. These results were robust to extensive sensitivity analyses.InterpretationFor most patients with type 2 diabetes that is inadequately controlled with metformin monotherapy, the addition of a sulphonylurea represents the most cost-effective second-line therapy.
| S-EPMC3216433 | biostudies-literature
Project description:AimTo assess time to insulin initiation among patients with type 2 diabetes mellitus (T2DM) treated with sitagliptin versus sulphonylurea as add-on to metformin.MethodsThis retrospective cohort study used GE Centricity electronic medical records and included patients aged ≥18 years with continuous medical records and an initial prescription of sitagliptin or sulphonylurea (index date) with metformin for ≥90 days during 2006-2013. Sitagliptin and sulphonylurea users were matched 1 : 1 using propensity score matching, and differences in insulin initiation were assessed using Kaplan-Meier curves and Cox regression. We used conditional logistic regression to examine the likelihood of insulin use 1-6 years after the index date for each year.ResultsPropensity score matching produced 3864 matched pairs. Kaplan-Meier analysis showed that sitagliptin users had a lower risk of insulin initiation compared with sulphonylurea users (p = 0.003), with 26.6% of sitagliptin users initiating insulin versus 34.1% of sulphonylurea users over 6 years. This finding remained significant after adjusting for baseline characteristics (hazard ratio 0.76, 95% confidence interval 0.65-0.90). Conditional logistic regression analyses confirmed that sitagliptin users were less likely to initiate insulin compared with sulphonylurea users [odds ratios for years 1-6: 0.77, 0.79, 0.81, 0.57, 0.29 and 0.75, respectively (p < 0.05 for years 4 and 5)].ConclusionsIn this real-world matched cohort study, patients with T2DM treated with sitagliptin had a significantly lower risk of insulin initiation compared with patients treated with sulphonylurea, both as add-on to metformin.
| S-EPMC5033027 | biostudies-literature
Project description:AimsCanagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM). This randomised, double-blind, placebo-controlled, Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM.MethodsPatients (N = 469) received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period and a 26-week extension. Prespecified primary end-point was change in HbA1c at 26 weeks. Secondary end-points included change in HbA1c at week 52 as well as proportion of patients achieving HbA1c < 7.0%, change in fasting plasma glucose (FPG) and systolic blood pressure, and per cent change in body weight, high-density lipoprotein cholesterol, and triglycerides (weeks 26 and 52).ResultsHbA1c was significantly reduced with canagliflozin 100 and 300 mg vs. placebo at week 26 (-0.85%, -1.06%, and -0.13%; p < 0.001); these reductions were maintained at week 52 (-0.74%, -0.96%, and 0.01%). Both canagliflozin doses reduced FPG and body weight vs. placebo at week 26 (p < 0.001) and week 52. Overall adverse event (AE) rates were similar across groups over 52 weeks, with higher rates of genital mycotic infections and osmotic diuresis-related AEs seen with canagliflozin vs. placebo; these led to few discontinuations. Increased incidence of documented, but not severe, hypoglycaemia episodes was seen with canagliflozin vs. placebo.ConclusionsCanagliflozin improved glycaemic control, reduced body weight, and was generally well tolerated in T2DM patients on metformin plus sulphonylurea over 52 weeks.
| S-EPMC4282288 | biostudies-literature
Project description:To investigate the cost-effectiveness of liraglutide as add-on to metformin vs. glimepiride or sitagliptin in patients with Type 2 diabetes uncontrolled with first-line metformin.Data were sourced from a clinical trial comparing liraglutide vs. glimepiride, both in combination with metformin, and a clinical trial comparing liraglutide vs. sitagliptin, both as add-on to metformin. Only the subgroup of patients in whom liraglutide was added to metformin monotherapy was included in the cost-utility analysis. The CORE Diabetes Model was used to simulate outcomes and costs with liraglutide 1.2 and 1.8 mg vs. glimepiride and vs. sitagliptin over patients' lifetimes. Treatment effects were taken directly from the trials. Costs and outcomes were discounted at 3.5% per annum and costs were accounted from a third-party payer (UK National Health System) perspective.Treatment with liraglutide 1.2 and 1.8 mg resulted, respectively, in mean increases in quality-adjusted life expectancy of 0.32 ± 0.15 and 0.28 ± 0.14 quality-adjusted life years vs. glimepiride, and 0.19 ± 0.15 and 0.31 ± 0.15 quality-adjusted life years vs. sitagliptin, and was associated with higher costs of £ 3003 ± £ 678 and £ 4688 ± £ 639 vs. glimepiride, and £ 1842 ± £ 751 and £ 3224 ± £ 683 vs. sitagliptin, over a patient's lifetime. Both liraglutide doses were cost-effective, with incremental cost-effectiveness ratios of £ 9449 and £ 16,501 per quality-adjusted life year gained vs. glimepiride, and £ 9851 and £ 10,465 per quality-adjusted life year gained vs. sitagliptin, respectively.Liraglutide, added to metformin monotherapy, is a cost-effective option for the treatment of Type 2 diabetes in a UK setting.
| S-EPMC3378710 | biostudies-literature
Project description:OBJECTIVE:To assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING:Investigator-initiated, randomised, placebo-controlled trial with a 2 × 3 factorial design conducted at eight hospitals in Denmark. PARTICIPANTS AND INTERVENTIONS:412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ? 7.5% (? 58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1 g twice daily) versus placebo, aiming at an HbA1c ? 7.0% (? 53 mmol/mol). OUTCOMES:The primary outcome was change in the mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight and hypoglycaemic and serious adverse events were other prespecified outcomes. RESULTS:Change in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI -0.003 to 0.026), p=0.11). HbA1c was more reduced in the metformin group (between-group difference -0.42% (95% CI -0.62% to -0.23%), p<0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p<0.001). The metformin group gained less weight (between-group difference -2.6 kg (95% CI -3.3 to -1.8), p<0.001). The groups did not differ with regard to number of patients with severe or non-severe hypoglycaemic or other serious adverse events, but the metformin group had more non-severe hypoglycaemic episodes (4347 vs 3161, p<0.001). CONCLUSIONS:Metformin in combination with insulin did not reduce carotid IMT despite larger reduction in HbA1c, less weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER:NCT00657943; Results.
| S-EPMC4771973 | biostudies-literature
Project description:There is currently a lack of evidence from direct comparisons of treatment outcomes with lixisenatide versus neutral protamine Hagedorn (NPH)-insulin in type 2 diabetes mellitus (T2DM) patients with suboptimal glycaemic control with oral antidiabetic drugs (OADs). Hence, the current analysis indirectly compared available evidence on the risk of hypoglycaemia and weight change between lixisenatide and NPH-insulin based on randomized controlled trial (RCT) data with exenatide, insulin glargine and placebo as common references.A systematic search of PubMed, Embase, the Cochrane database and clinical registries identified English- and German-language articles published from January 1980 to October 2012 reporting data from RCTs. Only publications of trials that reported outcomes from 24 to 30 weeks comparing glucagon-like peptide-1 receptor agonists or basal insulin versus another antidiabetic agent or placebo were included. Hypoglycaemia, patients at glycated haemoglobin (HbA1c) target and discontinuations due to adverse events (AEs) were treated as binary variables, with risk ratios and odds ratios (ORs) calculated. HbA1c and body weight were treated as continuous variables with difference in mean change from baseline (MD) calculated. Meta-analyses were performed with random effects models and indirect comparisons were performed according to Bucher's method.Seven RCTs (n=3,301 patients) comparing the efficacy and safety of lixisenatide, exenatide, insulin glargine and NPH-insulin with different antidiabetic treatments in adult patients with T2DM were included in the final analysis. In the adjusted indirect comparison, there was a significant difference in symptomatic hypoglycaemia (OR = 0.38; 95% CI = [0.17, 0.85]) and in confirmed hypoglycaemia (OR = 0.46; 95% CI = [0.22, 0.96]) favouring lixisenatide over NPH-insulin and comparable changes in HbA1c from baseline (MD = 0.07%; 95% CI = [-0.26%, 0.41%]). In contrast to NPH-insulin, there was a significant reduction in body weight with lixisenatide (MD = -3.62 kg; 95% CI = [-5.86 kg, -1.38 kg]) at study completion. The number of discontinuations due to AEs numerically favoured NPH-insulin over lixisenatide (OR = 2.64; 95% CI = [0.25, 27.96]), with a broad confidence interval.Lixisenatide treatment was associated with a lower risk of hypoglycaemia and a greater weight loss compared with NPH-insulin. Glycaemic control with lixisenatide treatment was comparable with NPH-insulin. These data suggest that lixisenatide is a beneficial treatment option for T2DM patients with inadequate glycaemic control on OADs, and is associated with reduced risk of hypoglycaemia and weight gain.
| S-EPMC4202665 | biostudies-literature
Project description:Background. Metformin is a widely accepted first-line pharmacotherapy for patients with type 2 diabetes mellitus (T2DM). Treatment of T2DM with glibenclamide, saxagliptin, or one of the other second-line treatment agents is recommended when the first-line treatment (metformin) cannot control the disease. However, there is little evidence on the additional cost and cost-effectiveness of adding second-line drugs. Therefore, this study aimed to estimate the cost-effectiveness of saxagliptin and glibenclamide as second-line therapies added to metformin compared with metformin only in T2DM in Ethiopia. Methods. This cost-effectiveness study was conducted in Ethiopia using a mix of primary data on cost and best available data from the literature on the effectiveness. We measured the interventions' cost from the providers' perspective in 2019 US dollars. We developed a Markov model for T2DM disease progression with five health states using TreeAge Pro 2020 software. Disability-adjusted life year (DALY) was the health outcome used in this study, and we calculated the incremental cost-effectiveness ratio (ICER) per DALY averted. Furthermore, one-way and probabilistic sensitivity analysis were performed. Results. The annual unit cost per patient was US$70 for metformin, US$75 for metformin + glibenclamide, and US$309 for metformin + saxagliptin. The ICER for saxagliptin + metformin was US$2259 per DALY averted. The ICER results were sensitive to various changes in cost, effectiveness, and transition probabilities. The ICER was driven primarily by the higher cost of saxagliptin relative to glibenclamide. Conclusion. Our study revealed that saxagliptin is not a cost-effective second-line therapy in patients with T2DM inadequately controlled by metformin monotherapy based on a gross domestic product per capita per DALY averted willingness-to-pay threshold in Ethiopia (US$953).
| S-EPMC8111283 | biostudies-literature