Among older US adults with type 2 diabetes, starting incretin-based therapy was not associated with higher 3-year risk than starting SGLT-2 inhibitors.
Evidence
A weighted Medicare new-user cohort compared 73,388 GLP-1RA users and 106,274 DPP-4 inhibitor users with SGLT-2 inhibitor users, finding adjusted 3-year risk differences of -23 and -2 thyroid cancer cases per 10,000, respectively, with confidence intervals crossing zero.
Caveat
Median treatment lasted only 0.82-1.15 years, so the study offers short-term reassurance but cannot rule out long-term or subtype-specific thyroid cancer risks.
Simplified
INTRODUCTION: Preclinical studies suggest a potential link between glucagon-like peptide 1 receptor agonists (GLP-1RA) and (TC), yet it is unclear if this risk translates to humans.
RESEARCH DESIGN AND METHODS: We estimated the comparative effect of incretin-based therapies (GLP-1RA and dipeptidyl-peptidase-4 inhibitors (DPP-4i)) versus sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on TC incidence among US older adults with type 2 diabetes. We defined TC as a thyroidectomy followed by ≥2 separate diagnoses codes for malignant neoplasm of thyroid gland within 90 days. We estimated adjusted 3-year cumulative risk differences of TC (aRDs) with 95% CIs using weighted Kaplan-Meier survival functions, and adjusted HRs using weighted Cox models.
RESULTS: We included 73 388 new users in the GLP-1RA versus SGLT-2i cohort (mean age 72.4 years, men: 48.3%) and 106 274 in the DPP-4i versus SGLT-2i cohort (mean age 74.6 years, men: 44.9%). At 3 years and a median duration of treatment of 0.82-1.15 years, the aRD for GLP-1RA versus SGLT-2i for TC was -23 per 10 000 (95% CI: -51 to 4) and the aRD for DPP-4i versus SGLT-2i was -2 per 10 000 (95% CI: -17 to 13). Secondary and sensitivity analyses were consistent.
CONCLUSIONS: Our study of US Medicare beneficiaries with type 2 diabetes suggests that the initiation of incretin-based therapies may not increase the 3-year risk of TC compared with initiation of SGLT-2i. This finding offers reassurance for short-term use but does not eliminate the possibility of increased long-term or subtype-specific risks.
Key numbers
-23 per 10 000
Adjusted 3-Year for vs.
Adjusted cumulative incidence difference for
-2 per 10 000
Adjusted 3-Year for vs.
Adjusted cumulative incidence difference for
Full Text
We can’t show the full text here under this license.
Competing interests: TS owns stock in Novartis, Roche, and Novo Nordisk. JBB reports research support from Corcept, Dexcom, and Novo Nordisk; consulting fees from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns, Vertex, Zealand; stock options from Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. KRK received consulting fees from Novo Nordisk. KRK has received personal compensation for consultation from Novo Nordisk. Additionally, KRK has received research-related contracts (paid to the institution) from NCATS, Bayer, Boehringer-Ingelheim, Carmot, Diasome, Eli Lilly, Novo Nordisk, Rhythm Pharmaceuticals, and vTv Therapeutics. TW is supported by American Diabetes Association grant #4-22-PDFPM-06.
