163-OR: Hypoglycemia with Glimepiride vs. Insulin Glargine in the GRADE Study

• Published in: Diabetes (New York, N.Y.) Vol. 71; no. Supplement_1
• Main Authors: PHILLIPS, LAWRENCE S., SEAQUIST, ELIZABETH R., BAKER, CHELSEA, BERGENSTAL, RICHARD M., BUTERA, NICOLE M., CRANDALL, JILL P., GOLAND, ROBIN, HOX, SOPHIA H., HSIA, DANIEL S., JOHNSON, MARY L., KAZEMI, ERIN, RASKIN, PHILIP, VALENCIA, WILLY, WALTJE, ANDREA H., YOUNES, NAJI
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01-06-2022
• Subjects: Blood glucose; Diabetes; Diabetes mellitus (non-insulin dependent); Drug dosages; Hypoglycemia; Insulin; Metformin; Patients
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db22-163-OR

Hypoglycemia limits the glycemic control that can be achieved with insulin and sulfonylureas (SUs) , but we lack evidence from head-to-head studies to guide management. In the GRADE comparative effectiveness study, 5,047 patients with type 2 diabetes (T2DM) of <years’ duration, on metformin monotherapy with HbA1c 6.8-8.5%, were randomized to addition of the SU glimepiride, insulin glargine U-100, sitagliptin, or liraglutide, permitting a direct comparison over 5.0 ± 1.3 (mean ± SD) years of follow-up. Glimepiride was initiated at 1-2 mg/day, glargine at 10-20 units/day, and both were titrated according to algorithms based on self-monitored blood glucose levels. Over 4 years, adjudicated severe hypoglycemia occurred in 2.3% of those randomized to glimepiride vs. 1.4% with glargine, but was less frequent with liraglutide (0.9%) and sitagliptin (0.7%) , p=0.003. During GRADE, HbA1c was measured every 3 months, and if a HbA1c >7.5% was confirmed, “rescue treatment” with glargine and/or aspart was added. We examined management in participants who were unable to keep HbA1c ≤7.5% - whose primary study drug was insufficient - prior to their “rescue”. At 3 mo after randomization, hypoglycemic symptoms or a measured glucose <70 mg/dl within the previous 30 d was reported by 33% of those using glimepiride vs. 15% with glargine (p <0.001) . The mean dose of glimepiride at 3 mo (n=627) and 12 mo (n=337) was 3.4 and 4.2 mg/day, respectively [a 24% increase but considerably submaximal (8 mg) ]. In contrast, the dose of glargine at 3 mo (n=487) and 12 mo (n=337) was 26 and 37 units/day, respectively (a 44% increase, p <0.0vs. glimepiride) . The outcome of a confirmed HbA1c >7.5% was reached in 50% of those using glimepiride, vs. 39% with glargine (p<0.001) . Conclusions: In metformin-treated patients with T2DM, there was more hypoglycemia, less increase in drug dose, and less preservation of glycemic control, with addition of the SU glimepiride compared to glargine; increases in glimepiride dose might have been limited by hypoglycemia.
Disclosure
L.S. Phillips: Research Support; Abbott Diabetes, AbbVie Inc., Janssen Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC, Pfizer Inc. Other Relationship; Cystic Fibrosis Foundation, Diasyst Inc. E.R. Seaquist: None. C. Baker: None. R.M. Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S. Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc. Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. N.M. Butera: None. J.P. Crandall: Research Support; Abbott. R. Goland: None. S.H. Hox: None. D.S. Hsia: None. M.L. Johnson: Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, Lilly, Medtronic, Novo Nordisk, Sanofi. P. Raskin: None. W. Valencia: None. A.H. Waltje: None. N. Younes: None.
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246, U34-DK-088043)