T1DM: safety and efficacy of short-acting exenatide for glycaemic control

Takeaway

• In patients with type 1 diabetes mellites (T1DM), the addition of short-acting exenatide to standard insulin therapy for 26-weeks was not associated with a reduction in glycated haemoglobin A1c (HbA1c) level, post-prandial glycaemic excursions, and glycaemic variability.
• Exenatide reduced bodyweight and prandial and total insulin requirements without increasing the risk for hypoglycaemia.

Why this matters

• Findings suggest short-acting exenatide does not seem to have a future as a standard add-on treatment to insulin therapy in T1DM.
• However, future studies are warranted to determine whether patients with T1DM (those with overweight or obesity and severe postprandial hyperglycaemia requiring high prandial insulin doses) may benefit from exenatide therapy.

Study design

• MAG1C trial included 105 patients with T1DM who received multiple daily insulin injections and were randomly assigned to receive subcutaneous exenatide (10μg; n=52) or placebo (n=53) for 26-weeks.
• Main outcome: between-group difference in HbA1c level after 26-weeks.
• Funding: AstraZeneca.

Key results

• After 26 weeks, no significant difference was observed between exenatide and placebo in:
  • HbA1c level (estimated treatment difference [ETD], -1.1 mmoL/moL; 95% CI, -3.4 to 1.2; P=.36);
  • mean amplitude of glycaemic excursion (ETD, 0.7; 95% CI, -0.2 to 1.6; P=.47); and
  • continuous overall net glycaemic action for 60 min (ETD, 0.1; 95% CI, -0.5 to 0.7; P=.96).
• After 26-weeks, exenatide vs placebo significantly reduced:
  • total insulin requirement (ETD, -9.0 [95% CI, -5.9 to -12.1] units/day P<.0001);
  • prandial insulin dose (ETD, -8.5 [95% CI, -11.2 to -5.7] units/day; P<.0001); and
  • body weight (ETD, 4.4 [95% CI, -5·4 to -3·3] kg; P<.001).
• The risk for severe, prolonged, and postprandial hypoglycaemia and lowered hypoglycaemia awareness did not differ between exenatide and placebo group.
• Compared with the placebo group, the incidences of gastrointestinal adverse event (48 vs 9) were higher, and incidences of serious adverse event (2 vs 6) were lower in the exenatide group.

Limitations

• Small sample size.