INTRODUCTION Although metformin is recommended as a first-line treatment for patients with type 2 diabetes (T2D) in Western countries, no specific treatment is recommended in Japan, and various agents are used. Metformin has long been used at low doses in Japan, and information regarding its effect at the maximum maintenance dose is lacking. Here, we compared the efficacy and safety of metformin at 1500 mg/day with those of the other oral anti-diabetic drugs (OADs) approved in Japan. METHODS Randomized controlled trials comparing a change in hemoglobin A1c (HbA1c) from baseline at 12 weeks or later (ΔHbA1c) among OADs (including placebo) as a first-line treatment in adult patients with T2D were selected by systematic review with comprehensive searching of CENTRAL, MEDLINE, Ichushi Web, and EMBASE and manual searching of clinical trial registries. The ΔHbA1c and incidence of hypoglycemia were compared among OAD treatments using Bayesian network meta-analysis (NMA). The relative risk (RR) of the incidence of hypoglycemia was determined relative to that of placebo. RESULTS Forty-six randomized controlled trials were identified in the systematic review, and 37 studies, comprising 38 different types of treatments, including placebos, were selected for the NMA of ΔHbA1c. Compared with metformin 1500 mg/day, 20 OAD treatments were significantly less effective in reducing HbA1c from baseline (differences from metformin 1500 mg/day: 0.40-0.96%). Two treatments (glimepiride 2 mg/day and pioglitazone 45 mg/day) showed greater mean reductions in HbA1c from baseline than metformin 1500 mg/day (- 0.38% and - 0.03%), although these differences were not significant. Regarding the incidence of hypoglycemia, only pioglitazone 30 mg/day among 31 treatments showed a lower RR (< - 0.01), whereas 23 treatments showed a significantly higher RR (1.02-66.71) than metformin 1500 mg/day. CONCLUSION The NMA suggested a preferable efficacy and safety profile of metformin 1500 mg/day compared with the other OADs approved in Japan.

Efficacy and Safety of Metformin Versus the Other Oral Antidiabetic Drugs in Japanese Type 2 Diabetes Patients: A Network Meta-analysis.

Objective The influence of dipeptidyl peptidase-4 (DPP4) inhibitors on glycemic variability compared to other oral antidiabetic drugs (OADs), measured based on the mean amplitude of glycemic excursions (MAGE), has not been comprehensively analyzed. The aim of the study was to perform a meta-analysis to compare the effects of DPP4 inhibitors on MAGE with other OADs in type 2 diabetes mellitus (T2DM) patients without concurrent insulin treatments. Methods The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant randomized controlled trials (RCTs). Study characteristics and outcome data were independently extracted by two authors. A random-effect model was used to combine the results. Results Fourteen studies with 855 patients were included. Compared to other OADs, DPP4 inhibitors significantly reduced MAGE (mean difference [MD]: -0.69 mmol/L, 95% confidence interval [CI]: -0.95 to -0.43, P&amp;lt;0.001) with mild heterogeneity (I 2 = 28%). Predefined subgroup analyses suggested that DPP4 inhibitors were more effective in reducing MAGE compared to insulin secretagogues (MD: -0.92 mmol/L, P&amp;lt;0.001) and non-secretagogues (MD: -0.43 mmol/L, P=0.02), as well as compared to sulfonylureas (MD: -0.91 mmol/L, P&amp;lt;0.001) and sodium glucose cotransporter 2 inhibitors (MD: -0.67 mmol/L, P=0.03). Conclusions DPP4 inhibitors may significantly reduce glycemic variability compared to other oral anti-diabetic drugs, as evidenced by MAGE in T2DM patients with no concurrent insulin treatment. Systematic review registration INPLASY, registration number: INPLASY2021120113. 

Influence of dipeptidyl peptidase-4 inhibitors on glycemic variability in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

<title>Abstract</title> Background: Flash glucose monitoring (FGM) can improve diabetes management, but no randomised controlled trials (RCTs) of FGM have been undertaken in Indigenous Australian populations. This study aimed to assess the feasibility of performing a RCT of FGM in Indigenous Australians with type 2 diabetes. Methods: In this open-labelled pilot RCT, Indigenous adults with type 2 diabetes were randomised to FGM or standard care for 6 months. Eligible participants were being treated with injectable diabetes medications and had a glycosylated haemoglobin (HbA1c) ≥ 7.0%. The feasibility outcome was the proportion of participants completing the trial. The preliminary effective outcome was the change in HbA1c. Secondary effectiveness outcomes included a change in time spent in target blood glucose; safety (hypoglycaemic episodes); and quality of life (EuroQol 5-Dimension 3-Level (EQ-5D-3L) score). Results: Of 126 screened individuals, 74 were eligible, 40 (31.7%) were randomised and 39 (97.5%) completed the study. Participants’ baseline characteristics were similar between the FGM and usual care groups, except for sex and body mass index. There were no between-group differences for: change in HbA1c; percentage of time spent in target blood glucose, low glucose and high glucose; or EQ-5D-3L scores. No severe hypoglycaemic episodes occurred. Conclusions: This is the first pilot RCT of FGM in Indigenous Australians with type 2 diabetes. The results support a larger RCT, which is currently in progress. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR12621000021875), retrospectively registered on 14 January 2021. 

Flash glucose monitoring for Indigenous Australians with type 2 diabetes: a randomised pilot and feasibility study

Relationship between glucose variability evaluated by continuous glucose monitoring and clinical factors, including glucagon-stimulated insulin secretion in patients with type 2 diabetes.

Effects of linagliptin vs. voglibose on daily glucose excursions during continuous glucose monitoring of Japanese type 2 diabetes patients (L-CGM): A randomized, open-label, two-arm, parallel comparative trial.

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Effects of linagliptin vs. voglibose on daily glucose excursions during continuous glucose monitoring of Japanese type 2 diabetes patients (L-CGM): A randomized, open-label, two-arm, parallel comparative trial.