Comparative Cardiovascular Effectiveness and Safety of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors According to Frailty in Type 2 Diabetes.

Publisher: American Diabetes Association Country of Publication: United States NLM ID: 7805975 Publication Model: Print Cited Medium: Internet ISSN: 1935-5548 (Electronic) Linking ISSN: 01495992 NLM ISO Abbreviation: Diabetes Care Subsets: MEDLINE

Publication: Alexandria Va : American Diabetes Association
Original Publication: New York, American Diabetes Assn.

Diabetes Mellitus, Type 2*/epidemiology ; Dipeptidyl-Peptidase IV Inhibitors*/adverse effects ; Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use ; Frailty* ; Myocardial Infarction*; Aged ; Humans ; United States ; Hypoglycemic Agents/adverse effects ; Glucagon-Like Peptide-1 Receptor/agonists ; Medicare

Objective: To evaluate the comparative cardiovascular effectiveness and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is) in older adults with type 2 diabetes (T2D) across different frailty strata.
Research Design and Methods: We performed three 1:1 propensity score-matched cohort studies, each stratified by three frailty strata, using data from Medicare beneficiaries (2013-2019) with T2D who initiated SGLT-2is, GLP-1RAs, or DPP-4is. In time-to-event analyses, we assessed the primary cardiovascular effectiveness composite outcome of acute myocardial infarction, ischemic stroke, hospitalization for heart failure, and all-cause mortality. The primary safety outcome was a composite of severe adverse events that have been linked to SGLT-2i or GLP-1RA use.
Results: Compared with DPP-4is, the overall hazard ratio (HR) for the primary effectiveness outcome associated with SGLT-2is (n = 120,202 matched pairs) was 0.72 (95% CI 0.69-0.75), corresponding to an incidence rate difference (IRD) of -13.35 (95% CI -15.06 to -11.64). IRD ranged from -6.74 (95% CI -8.61 to -4.87) in nonfrail to -27.24 (95% CI -41.64 to -12.84) in frail people (P for interaction < 0.01). Consistent benefits were observed for GLP-1RAs compared with DPP-4is (n = 113,864), with an overall HR of 0.74 (95% CI 0.71-0.77) and an IRD of -15.49 (95% CI -17.46 to -13.52). IRD in the lowest frailty stratum was -7.02 (95% CI -9.23 to -4.81) and -25.88 (95% CI -38.30 to -13.46) in the highest (P for interaction < 0.01). Results for SGLT-2is versus GLP-1RAs (n = 89,865) were comparable. Severe adverse events were not more frequent with SGLT-2is or GLP-1RAs than DPP-4is.
Conclusions: SGLT-2is and GLP-1RAs safely improved cardiovascular outcomes and all-cause mortality, with the largest absolute benefits among frail people.
(© 2023 by the American Diabetes Association.)

N Engl J Med. 2011 Mar 3;364(9):818-28. (PMID: 21366473)
Stroke. 2002 Oct;33(10):2465-70. (PMID: 12364739)
J Gerontol A Biol Sci Med Sci. 2020 May 22;75(6):1120-1125. (PMID: 31566201)
JAMA Cardiol. 2021 Feb 1;6(2):148-158. (PMID: 33031522)
N Engl J Med. 2017 Aug 17;377(7):644-657. (PMID: 28605608)
J Clin Epidemiol. 2011 Jul;64(7):749-59. (PMID: 21208778)
Pharmacoepidemiol Drug Saf. 2010 Jun;19(6):596-603. (PMID: 20140892)
J Pers Med. 2022 Nov 16;12(11):. (PMID: 36422087)
Lancet Diabetes Endocrinol. 2019 Oct;7(10):776-785. (PMID: 31422062)
J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. (PMID: 11253156)
Circulation. 2022 Oct 18;146(16):1210-1224. (PMID: 36029465)
N Engl J Med. 2022 Sep 22;387(12):1089-1098. (PMID: 36027570)
Lancet Diabetes Endocrinol. 2020 Oct;8(10):855-867. (PMID: 32946822)
Am Heart J. 2004 Jul;148(1):99-104. (PMID: 15215798)
BMJ. 1999 Dec 4;319(7223):1492-5. (PMID: 10582940)
Am J Epidemiol. 2018 Sep 1;187(9):1951-1961. (PMID: 29750409)
J Am Geriatr Soc. 2020 Aug;68(8):1771-1777. (PMID: 32274807)
J Gerontol A Biol Sci Med Sci. 2004 Mar;59(3):255-63. (PMID: 15031310)
Lancet Healthy Longev. 2020 Dec;1(3):e106-e116. (PMID: 33313578)
Diabetes Care. 2021 Mar;44(3):826-835. (PMID: 33495295)
Ann Intern Med. 2021 Sep;174(9):1214-1223. (PMID: 34280330)
J Gen Intern Med. 2020 May;35(5):1516-1522. (PMID: 32072368)
Diabetes Obes Metab. 2018 Apr;20(4):974-984. (PMID: 29206336)
Diabetes Care. 2022 Jan 1;45(Suppl 1):S195-S207. (PMID: 34964847)
Ann Pharmacother. 2016 Sep;50(9):741-6. (PMID: 27307411)
JAMA Intern Med. 2022 May 1;182(5):513-519. (PMID: 35344001)
J Clin Med. 2022 Mar 19;11(6):. (PMID: 35330032)
Pharmacoepidemiol Drug Saf. 2012 Jan;21 Suppl 1:129-40. (PMID: 22262599)
Ann Intern Med. 2022 Jun;175(6):820-830. (PMID: 35467935)
J Diabetes Complications. 2020 Sep;34(9):107639. (PMID: 32595017)
Diabetes Care. 2021 Jan;44(Suppl 1):S168-S179. (PMID: 33298423)
N Engl J Med. 2022 Sep 22;387(12):1075-1088. (PMID: 36129997)
BMJ. 2018 Nov 14;363:k4365. (PMID: 30429124)
J Gerontol A Biol Sci Med Sci. 2018 Jun 14;73(7):980-987. (PMID: 29244057)
N Engl J Med. 2019 Nov 21;381(21):1995-2008. (PMID: 31535829)
Diabetes Obes Metab. 2021 Oct;23(10):2320-2328. (PMID: 34169619)
Diabetes Ther. 2021 May;12(5):1227-1247. (PMID: 33830409)

K08 AG055670 United States AG NIA NIH HHS; U01 FD007213 United States FD FDA HHS

0 (Dipeptidyl-Peptidase IV Inhibitors)
0 (Sodium-Glucose Transporter 2 Inhibitors)
0 (Hypoglycemic Agents)
0 (Glucagon-Like Peptide-1 Receptor)

Date Created: 20230907 Date Completed: 20231030 Latest Revision: 20240210

20240210

PMC10620535

10.2337/dc23-0671

37677118