Bo Ri Kim, Mercer University College of Pharmacy.
According to 2015 American Diabetes Association (ADA) Diabetes Guidelines, metformin is recommended for type-2 diabetes patients with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or A1C 5.7-6.4%. It also recommends use metformin with insulin to reduce insulin dose requirements and improve metabolic control in overweight patients with type-1 diabetes patients. 
|Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes |
|Design||Multicenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial; N= 140|
|Objective||To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type-1 diabetes|
|Study Groups||Studied 140 adolescents aged 12.1 to 19.6 years with mean type-1 diabetes duration seven years, mean total daily insulin 1.1 U/kg, and mean HbA1c 8.8%|
|Methods||· Randomization to receive metformin (n = 71) or placebo (n = 69)
· The daily dose of study drug was increased over four weeks as follows: one tablet in the evening for seven days, one tablet twice daily for seven days, one tablet in the morning and one tablet at night for seven days; and then two tablets in the morning and two tablets at night daily (2000 mg) for the remainder of the 26-week treatment period.
|Primary Outcome Measure||Change in HbA1c level from baseline|
|Baseline Characteristics||Characteristics, n (%)||Metformin||Placebo|
|Female||44 (62)||48 (70)|
|Age, mean||15.4 (1.7)||15.1 (1.8)|
|White||51 (72)||52 (75)|
|Black||4 (6)||5 (7)|
|Hispanic or Latino||13 (18)||11 (16)|
|Duration of diabetes (year)||7.5 (3.6)||6.4 (3.0)|
|Overweight||36 (51)||26 (38)|
|Glucose, mean||206 (35)||208 (34)|
|Total daily insulin, mean (U/kg per d)||1.1 (0.2)||1.1 (0.2)|
|Total basal/long-acting insulin, mean (U/kg per d)||0.5 (0.1)||0.5 (0.1)|
|Results||· Baseline HbA1c was 8.8% in each group. At 13-week follow-up, reduction in HbA1c was greater with metformin (−0.2%) than placebo (0.1%; mean difference, −0.3% [95% CI, −0.6% to 0.0%]; p = .02).
· However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, −0.3% to 0.3%]; p = .92).
|Adverse Events||Common Adverse Events: gastrointestinal events (50%)|
|Serious Adverse Events: diabetic ketoacidosis (4%), severe hypoglycemia (7%)|
|Study Author Conclusions||Among overweight adolescents with type 1-diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type-1 diabetes to improve glycemic control.|
This study failed to show the effect of metformin as an adjunctive therapy to basal-bolus insulin on glycemic control in overweight adolescents with type-1 diabetes. There were no statistically or clinically significant differences from baseline in glucose reports between two groups. However, metformin decreased weight gain, body mass index, fat, and total daily insulin dose.
- American Diabetes Association. Standards of medical care in diabetes-2015. Diabetes Care. 2015;38(suppl 1):S1-S93.
- Libman I, Miller K, Dimeglio L, et al. Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial. 2015 Dec 1;314(21):2241-50.