Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes

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. [1]

Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes [2]
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.

Duration Six months
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)
Race/ethnicity    
White 51 (72) 52 (75)
Black 4 (6) 5 (7)
Hispanic or Latino 13 (18) 11 (16)
Asian 2 (3) 0
Duration of diabetes (year) 7.5 (3.6) 6.4 (3.0)
Overweight 36 (51) 26 (38)
HbA1c, mean 8.8 8.8
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.

Reference:

  1. American Diabetes Association. Standards of medical care in diabetes-2015. Diabetes Care. 2015;38(suppl 1):S1-S93.
  2. 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.
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