Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)

Diabetes Care. 2024 Apr 1;47(4):610-619. doi: 10.2337/dc23-2459.

Abstract

Objective: We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments.

Research design and methods: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of <10 years' duration, HbA1c 6.8-8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined differences at 1 year and over the 3-year follow-up.

Results: Across treatments, diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001) decreased over 1 year. Diabetes distress was lower at 1 year for the glargine group than for the other groups combined (-0.10, P = 0.002). Diabetes distress was also lower for liraglutide than for glimepiride or sitagliptin (-0.10, P = 0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms.

Conclusions: Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress. Glargine lowered diabetes distress modestly at 1 year rather than increasing it. Liraglutide also reduced diabetes distress at 1 year. Results can inform treatment decisions for adults with early T2DM.

MeSH terms

  • Adult
  • Blood Glucose
  • Depression / drug therapy
  • Diabetes Mellitus, Type 2* / drug therapy
  • Drug Therapy, Combination
  • Female
  • Glucagon-Like Peptide 1
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin Glargine / therapeutic use
  • Liraglutide / therapeutic use
  • Male
  • Metformin* / therapeutic use
  • Middle Aged
  • Sitagliptin Phosphate / therapeutic use
  • Sulfonylurea Compounds*
  • Treatment Outcome

Substances

  • glimepiride
  • Liraglutide
  • Insulin Glargine
  • Glucagon-Like Peptide 1
  • Blood Glucose
  • Glycated Hemoglobin
  • Hypoglycemic Agents
  • Metformin
  • Sitagliptin Phosphate
  • Sulfonylurea Compounds