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

Background:The prevalence of overweight and obesity in type 1 diabetes mellitus (T1DM) individuals is increasing. Overweight people with T1DM may be insulin resistant. Glycaemic variability (GV) is an emerging measure of glycaemic control. The aim of this study is to investigate whether metformin, in adjunct to insulin, would have any favourable effect on GV. Methods:This was a multi-centre, open-label randomised crossover study. Twenty-four overweight/obese T1DM patients aged & GT;18 years old with HbA1c & GT; 7.0% (53 mmol/mol) were recruited and randomised into two study arms. For first 6-week, one arm remained on standard of care (SOC), the other arm received metformin, adjunctive to SOC. After 2-week washout, patients crossed over and continued for another 6 weeks. Glycaemic variability, other glycaemic parameters and metabolic profile were monitored. Results:There were significant reduction in metformin group for GV: mean (0.18 & PLUSMN; 1.73 vs -0.95 & PLUSMN; 1.24, p = 0.014), %CV (-15.84 (18.92) vs -19.08 (24.53), p = 0.044), glycemic risk assessment of diabetes equation (-0.69 (3.83) vs -1.61 (3.61), p = 0.047), continuous overlapping net glycaemic action (0.25 & PLUSMN; 1.62 vs -0.85 & PLUSMN; 1.22, p = 0.013), J-index (-0.75 (21.91) vs -7.11 (13.86), p = 0.034), time in range (1.13 & PLUSMN; 14.12% vs 10.83 & PLUSMN; 15.47%, p = 0.032); changes of systolic blood pressure (2.78 & PLUSMN; 11.19 mmHg vs -4.30 & PLUSMN; 9.81 mmHg, p = 0.027) and total daily dose (TDD) insulin (0.0 (3.33) units vs -2.17 (11.45) units, p = 0.012). Hypoglycaemic episodes were not significant in between groups. Conclusion:Metformin showed favourable effect on GV in overweight/obese T1DM patients and reduction in systolic blood pressure, TDD insulin, fasting venous glucose and fructosamine.