TY - JOUR
T1 - Glucose-Lowering Agents and the Risk of Hypoglycemia
T2 - a Real-world Study
AU - Lyu, Beini
AU - Hwang, Y. Joseph
AU - Selvin, Elizabeth
AU - Jameson, Brian C.
AU - Chang, Alex R.
AU - Grams, Morgan E.
AU - Shin, Jung Im
N1 - Funding Information:
Dr. Jung-Im Shin was supported by grant number K01DK121825 (Principal Investigator: J.S.) from the National Institute of Diabetes and Digestive and Kidney Diseases.
Funding Information:
Dr. Lyu has nothing to disclose. Dr. Hwang has nothing to disclose. Dr. Selvin reports grants from National Institutes of Health (NIH), during the conduct of the study; personal fees from Novo Nordisk, other from Wolters Kluwer, outside the submitted work. Dr. Jameson reports speakers bureau Sanofi Aventis — glargine, Soliqua, Boehringer Ingelheim — Jardiance. Dr. Chang reports grants from Novo Nordisk, personal fees from Reata, personal fees from Novartis, outside the submitted work. Dr. Grams reports grants from National Institute of Health, during the conduct of the study; grants from NIDDK, grants and other from NKF, other from ADA, non-financial support and other from KDIGO, other from USRDS, outside of submitted work. Dr. Shin reports grants from NIH, during the conduct of the study; grants from Merck, outside the submitted work.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Society of General Internal Medicine.
PY - 2023/1
Y1 - 2023/1
N2 - Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) are increasingly recommended in type 2 diabetes. Hypoglycemia is a serious adverse effect of glucose-lowering agents. Real-world comparison of hypoglycemic risks among SGLT2i, GLP1RA, dipeptidyl peptidase-4 inhibitor (DPP4i), and sulfonylureas is limited. Objective: Quantify the risk of hypoglycemia associated with SGLT2i, GLP1RA, DPP4i, and sulfonylureas (the primary reference group). Design: Retrospective cohort study conducted using electronic health records from Geisinger Health, Pennsylvania (2015–2019). Participants: A total of 10,713 patients with type 2 diabetes who newly received SGLT2i (n=1487), GLP1RA (n=1241), DPP4i (n=2938), or sulfonylureas (n=5047). Propensity score–based inverse probability of treatment weighting was used to balance patient characteristics across four treatment groups simultaneously. Main Measures: Hypoglycemia was defined as capillary blood glucose <70 mg/dL; severe hypoglycemia was defined as capillary blood glucose <54 mg/dL. A weighted Cox proportional hazards regression model was used to estimate the risk of outcomes for pairwise comparisons of SGTL2i, GLP1RA, DPP4i, and sulfonylureas. Key Results: Median follow-up was 21.3 months. Compared with sulfonylureas, the risk of hypoglycemia was lower with SGLT2i (hazard ratio 0.60 [95% confidence interval 0.48–0.75]), GLP1RA (0.49 [0.34–0.69]), and DPP4i (0.60 [0.48–0.78]). The risk of severe hypoglycemia was also lower with SGLT2i (0.43 [0.35–0.74]), GLP1RA (0.50 [0.28–0.87]), and DPP4i (0.64 [0.46–0.90]) compared to sulfonylureas. The risks of hypoglycemia and severe hypoglycemia were similar across the SGLT2i, GLP1RA, and DPP4i groups (SGLT2i vs. DPP4i: 0.95 [0.67–1.34]; GLP1RA vs. DPP4i: 0.81 [0.55–1.19]; SGLT2i vs. GLP1RA: 1.17 [0.76–1.82] for hypoglycemia). Conclusion: SGLT2i and GLP1RA confer a lower risk of hypoglycemia compared with sulfonylureas and similar risk compared with DPP4i. Given the known cardiovascular benefits associated with SGLT2i and GL1PRA, our results suggesting the safety of SGLT2i and GL1PRA further support their use.
AB - Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) are increasingly recommended in type 2 diabetes. Hypoglycemia is a serious adverse effect of glucose-lowering agents. Real-world comparison of hypoglycemic risks among SGLT2i, GLP1RA, dipeptidyl peptidase-4 inhibitor (DPP4i), and sulfonylureas is limited. Objective: Quantify the risk of hypoglycemia associated with SGLT2i, GLP1RA, DPP4i, and sulfonylureas (the primary reference group). Design: Retrospective cohort study conducted using electronic health records from Geisinger Health, Pennsylvania (2015–2019). Participants: A total of 10,713 patients with type 2 diabetes who newly received SGLT2i (n=1487), GLP1RA (n=1241), DPP4i (n=2938), or sulfonylureas (n=5047). Propensity score–based inverse probability of treatment weighting was used to balance patient characteristics across four treatment groups simultaneously. Main Measures: Hypoglycemia was defined as capillary blood glucose <70 mg/dL; severe hypoglycemia was defined as capillary blood glucose <54 mg/dL. A weighted Cox proportional hazards regression model was used to estimate the risk of outcomes for pairwise comparisons of SGTL2i, GLP1RA, DPP4i, and sulfonylureas. Key Results: Median follow-up was 21.3 months. Compared with sulfonylureas, the risk of hypoglycemia was lower with SGLT2i (hazard ratio 0.60 [95% confidence interval 0.48–0.75]), GLP1RA (0.49 [0.34–0.69]), and DPP4i (0.60 [0.48–0.78]). The risk of severe hypoglycemia was also lower with SGLT2i (0.43 [0.35–0.74]), GLP1RA (0.50 [0.28–0.87]), and DPP4i (0.64 [0.46–0.90]) compared to sulfonylureas. The risks of hypoglycemia and severe hypoglycemia were similar across the SGLT2i, GLP1RA, and DPP4i groups (SGLT2i vs. DPP4i: 0.95 [0.67–1.34]; GLP1RA vs. DPP4i: 0.81 [0.55–1.19]; SGLT2i vs. GLP1RA: 1.17 [0.76–1.82] for hypoglycemia). Conclusion: SGLT2i and GLP1RA confer a lower risk of hypoglycemia compared with sulfonylureas and similar risk compared with DPP4i. Given the known cardiovascular benefits associated with SGLT2i and GL1PRA, our results suggesting the safety of SGLT2i and GL1PRA further support their use.
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U2 - 10.1007/s11606-022-07726-8
DO - 10.1007/s11606-022-07726-8
M3 - Article
C2 - 35831767
AN - SCOPUS:85134312534
SN - 0884-8734
VL - 38
SP - 107
EP - 114
JO - Journal of general internal medicine
JF - Journal of general internal medicine
IS - 1
ER -