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Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial.

ABSTRACT: Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia.This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed type 2 diabetes mellitus patients with glycated hemoglobin A1c (HbA1c) 8.5-12.0% were randomized to double-blind oral treatment with linagliptin/metformin or linagliptin monotherapy. The primary end-point was the change from baseline in HbA1c at week 24. We evaluated data for the 125 participants from Asian countries.After 24 weeks, the mean ± standard error reduction from baseline in HbA1c (mean 10.0%) was -2.99 ± 0.18% with linagliptin/metformin and -1.84 ± 0.18% with linagliptin; a treatment difference of -1.15% (95% confidence interval -1.65 to -0.66, P < 0.0001). HbA1c <7.0% was achieved by 60% of participants receiving linagliptin/metformin. The mean bodyweight change after 24 weeks was -0.45 ± 0.41 kg and 1.33 ± 0.45 kg in the linagliptin/metformin and linagliptin groups, respectively (treatment difference -1.78 kg [95% confidence interval -2.99 to -0.57, P = 0.0043]). Drug-related adverse events occurred in 9.7% of participants receiving linagliptin/metformin and 4.8% of those receiving linagliptin. Hypoglycemia occurred in 6.5% and 4.8% of the linagliptin/metformin and linagliptin groups, respectively, with no severe episodes. Gastrointestinal disorders occurred in 12.9% and 12.7% of the linagliptin/metformin and linagliptin groups, respectively, with no associated treatment discontinuations.In people from Asia with newly diagnosed type 2 diabetes mellitus and marked hyperglycemia, the initial combination of linagliptin and metformin substantially improved glycemic control without weight gain and with infrequent hypoglycemia. Initial oral combination therapy might be a viable treatment for such individuals.

SUBMITTER: Ma RC

PROVIDER: S-EPMC5934255 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial.

Ma Ronald Cw RC Del Prato Stefano S Gallwitz Baptist B Shivane Vyankatesh K VK Lewis-D'Agostino Diane D Bailes Zelie Z Patel Sanjay S Lee Jisoo J von Eynatten Maximilian M Di Domenico Maximiliano M Ross Stuart A SA

Journal of diabetes investigation 20170916

<h4>Aims/introduction</h4>Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia.<h4>Materials and methods</h4>This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly d ...[more]

PMID: 28921919

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Project description:The safety and efficacy of dipeptidyl peptidase-4 inhibitors in patients newly diagnosed type 2 diabetes mellitus (T2DM) with severe hyperglycaemia have remained to be sufficiently demonstrated. The aim of the present study was to determine whether sitagliptin combined with metformin as an initial treatment had non-inferior outcomes with regards to glycaemic remission and ?-cell function recovery to those of standard insulin therapy in this patient group. A prospective observational study was performed comparing the effects of sitagliptin combined with metformin and insulin therapy in a real-world clinical setting. A total of 168 participants were enrolled and received sitagliptin combined with metformin (Sig) or insulin (Ins) for almost 4 weeks. In addition, each group was further stratified into three subgroups, according to glycosylated haemoglobin (HbA1c) levels (<10, 10-12 and >12%). The primary outcomes were ?-cell function and changes in fasting plasma glucose (FPG) and HbA1c at the 3-month follow-up. Both insulin and sitagliptin combined with metformin reduced hyperglycaemia and achieved similar glycaemic outcomes, and no significant differences in FPG and HbA1c levels were obtained. No significant changes were observed in ?-cell function concomitant with the glucose-lowering effects of the treatments. Of note, participants in the Ins group exhibited weight gain, whereas those in the Sig group had weight loss, with significant differences becoming evident after 1 month, particularly in the HbA1c <10% subgroup. As compared with insulin injection, early treatment with sitagliptin combined with metformin in newly diagnosed patients with T2DM and severe hyperglycaemia produced non-inferior outcomes with regards to glycaemic remission. Therefore, combination of sitagliptin and metformin may be a viable initial treatment option for patients who prefer an alternative to insulin injection. This study was registered with ClinicalTrials.gov under no. NCT03180281.

Project description:There are multiple glucose-lowering drugs available as alternative initial monotherapy for type 2 diabetes patients with contraindications or intolerance to metformin. However, little comparative and systematic data are available for them as initial monotherapy. This study estimated and compared the treatment effects of glucose-lowering drugs as initial monotherapy for type 2 diabetes. PubMed, Web of Science, Embase, CNKI, Chongqing VIP, and WanFang Data from 1 January 1990 until 31 December 2020 were searched for randomized controlled trials which compared a glucose-lowering drug with placebo/lifestyle-intervention for type 2 diabetes. Drug classes included metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), glinides (NIDEs), α-glucosidase inhibitors (AGIs), dipeptidyl peptidase-4 inhibitors (DPP-4is), sodium-glucose cotransporter-2 inhibitors (SGLT2is), insulins (INSs), and glucagon-like peptide-1 receptor agonists (GLP-1RAs). A total of 185 trials were included, identifying 38,376 patients from 56 countries across six continents. When choosing an initial drug monotherapy alternative to metformin, SUs were most efficacious in reducing HbA1c (-1.39%; 95% CI -1.63, -1.16) and FPG (-2.70 mmol/L; 95% CI -3.18, -2.23), but increased hypoglycemia risks (5.44; 95% CI 2.11, 14.02). GLP-1RAs were most efficacious in reducing BMI (-1.05 kg/m2; 95% CI -1.81, -0.29) and TC (-0.42 mmol/L; 95% CI -0.61, -0.22). TZDs were most efficacious in increasing HDL-C (0.12 mmol/L; 95% CI 0.07, 0.17). SGLT2is were most efficacious in lowering SBP (-4.18 mmHg; 95% CI -4.84, -3.53). While AGIs conferred higher risk of AE-induced discontinuations (2.57; 95% CI 1.64, 4.03). Overall, only GLP-1RAs showed an integrated beneficial effect on all outcomes. Our results also confirmed the intraclass differences in treatment effects across drugs. Most trials were short-term, and no significant differences in mortality, total vascular events, myocardial infarction, heart failure, stroke, or diabetic nephropathy were observed across drug classes. Our results suggest a potential treatment hierarchy for decision-makers, with GLP-1RAs being the preferred alternative therapy to metformin regarding their favorable efficacy and safety profiles.

Dataset Information

Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial.

Publications

Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial.

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