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Can Metformin Lower A1c For Patients With Type 1 Diabetes?

Feb 17, 2018
 

Insulin resistance has been proposed as one of the causes of poor glycemic control in youth with type 1 diabetes who have excess weight or obesity.

To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in youth with T1D who have excess weight or obesity they did a 9-mo randomized, double-blind, placebo-controlled trial of metformin and placebo in 28 subjects (13m/15) of ages 10-20 years (y), with HbA1c >8% (64 mmol/mol), BMI >85%, and T1D > 12 months and was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 ± 2.5 y; while the control group was made up of 13 subjects (5m/ 8f), of age 14.5 ± 3.1y. All participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG) between 90-120 mg/dL (5.0-6.7 mmol/L). Pubertal maturation was determined by Tanner stage.

It was assumed that the metformin therapy will improve glycemic control in youth with T1D and excess weight or obesity, similar to those with type 2 diabetes.

Youth with type 1 diabetes (T1D) who have excess weight or obesity often have suboptimal glycemic control. Though insulin resistance has been proposed as one of the causes of this poor glycemic control, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.

Metformin is a biguanide, which acts principally by increasing insulin sensitivity in the liver by inhibiting hepatic gluconeogenesis and thereby reducing hepatic glucose output. Randomized controlled trials with metformin in adolescents with type 2 diabetes (T2D) reported a decrease in fasting plasma glucose concentration [3]. However, there have been conflicting reports from studies in adolescents with T1D. The benefit was transient in one study and no decrease was found in another. The main drawback of these studies was the small sample size and lack of reporting on long-term benefit and safety of adjunctive therapy in many of them.

To address this question, we conducted a 12-month clinical trial consisting of a 3-month run-in-phase and a 9-month randomized, double-blind, placebo-controlled interventional period to determine the role of adjunctive metformin therapy on glycemic control in youth with T1D who have excess weight or obesity. We hypothesized that adjunctive metformin therapy would improve glycemic control in youth with T1D who have excess weight or obesity. The study’s objective was to compare the effect of adjunctive metformin vs. placebo on glycemic control, body mass index (BMI), waist circumference (WC), total daily dose (TDD) of insulin, and hypoglycemia in youth with T1D who have excess weight or obesity receiving multiple daily injections of insulin.

Over the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4 for placebo versus 9.46% for metformin) was not significant (p = 0.903). There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin), (p = 0.927); total daily dose (TDD) of short-acting insulin per kg body weight/day(p = 0.936); and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin) (p = 0.221). There was no difference in the occurrence of hypoglycemia between the groups.

From the results it was concluded that, after 9-month RCT of adjunctive metformin therapy in youth with T1D who have excess weight or obesity resulted in a 0.4% lower HbA1c value in the metformin group compared to the placebo group.

Practice Pearls:

  • Metformin when used for patients with type 2 has been found to significantly reduce blood sugars and help to help to lose weight and to prevent weight gain when using insulin.
  • The use of metformin for those with type 1 diabetes was found to be not significant in reducing blood sugars compared to the placebo group.
  • The use of metformin for the purpose of losing weight has still yet to be determined.

Published in Diabetes, Journal Scan / Research · October 08, 2017