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)

• Published in: Diabetes care Vol. 47; no. 4; pp. 610 - 619
• Main Authors: Gonzalez, Jeffrey S, Bebu, Ionut, Krause-Steinrauf, Heidi, Hoogendoorn, Claire J, Crespo-Ramos, Gladys, Presley, Caroline, Naik, Aanand D, Kuo, Shihchen, Johnson, Mary L, Wexler, Deborah, Crandall, Jill P, Bantle, Anne E, Arends, Valerie, Cherrington, Andrea L
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-04-2024
• Subjects: Adult; Adults; Antidiabetics; Blood Glucose; Comparative studies; Depression - drug therapy; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Drug Therapy, Combination; Effectiveness; Effectiveness studies; Emotions; Female; Glucagon; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents - therapeutic use; Insulin; Insulin Glargine - therapeutic use; Liraglutide - therapeutic use; Male; Mental depression; Metformin; Metformin - therapeutic use; Middle Aged; Quality; Reduction; Reports from the GRADE Study; Research design; Sitagliptin Phosphate - therapeutic use; Sulfonylurea; Sulfonylurea Compounds; Treatment Outcome
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc23-2459

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.
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.
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.
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.