Metformin improves glycemic variability in adults with type 1 diabetes mellitus: an open-label randomized control trial

Abstract

Introduction: Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM. Objectives: In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored. Patients and methods: A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000- 2000 mg metformin daily add-on insulin (MET group, n=34) or insulin (Non-MET group, n=31). After, baseline measurements were repeated. Results: The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with Non-MET group [-1.58 (-3.35,0.31) mmol/L versus 1.36 (-1.12,2.24) mmol/L, P=0.004]. In parallel, the largest amplitude of glycemic excursions [-2.83 (-5.47,-0.06) mmol/L versus 0.45 (-1.29,4.48) mmol/L, P=0.004], the standard deviation of blood glucose [-0.85 (-1.51,0.01) mmol/L versus -0.14 (-0.68,1.21) mmol/L, P=0.015], and the coefficient of variation [-6.66 (-15.00,1.50) % versus -1.60 (-6.28,11.71) %, P=0.012] all demonstrated improvement in the MET group, compared with the Non-MET group. Significant reduction in insulin dose, body mass index and body weight were observed in patients in MET, not those in Non-MET group. Conclusion: Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.

Effects of metformin on glycaemic variability in combination with insulin in overweight/obese patients with type 1 diabetes

“…In a recent study of metformin effect on GV, the MAGE (primary outcome), standard deviation of blood glucose, largest amplitude of glycaemic excursions and CV demonstrated significant improvement in metformin group; patients with higher BMI presented greater reduction in MAGE and %CV. 26 In our study which involved overweight/obese patients, significant reduction in %CV was observed but not MAGE. Another study did not find any significant variation in GV.…”

“…However, our results were almost similar to a recent study, which reported 23.5% of adverse event in MET group. 26 Metformin is generally well-tolerated. This is a carefully designed and well-conducted clinical study to explore the effects of adjunct metformin treatment on GV in overweight/obese adults with T1DM.…”

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

“…The same study reported improvements in levels of proatherogenic lipid profiles, irrespective of previous background statin therapy [91]. Evidence from a small randomized-controlled study also suggests fewer glycemic fluctuations in metformin users with T1D [92].…”

The Beneficial Effects of a Multispecies Probiotic Supplement on Glycaemic Control and Metabolic Profile in Adults with Type 1 Diabetes: A Randomised, Double-Blinded, Placebo-Controlled Pilot-Study

“…All the patients were provided with the same dietary and physical activity guidance by the same dietician and diabetes educator before being randomly assigned a group. 12 …”