Three new classes of glucose-lowering drugs were introduced into practice over the past 15 years: DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors. These drugs have low hypoglycemia risk, do not cause weight gain, and post-marketing outcomes trials found cardiovascular and renal benefits associated with GLP-1RA and SGLT2i use.

Our objective was to determine whether these drugs are being used by patients with type 2 diabetes most likely to benefit from them. Using OptumLabs Data Warehouse, a de-identified dataset of commercially-insured and Medicare Advantage beneficiaries, we identified adults with type 2 diabetes who first started a DPP-4i (n=140,933), GLP-1RA (n=107,331), SGLT2i (n=112,892), or any other diabetes drug (n=1,743,484) between 2013-2018. After adjustment for age, gender, race/ethnicity, insurance type, baseline medications, year, prescriber specialty, and comorbidities, we found that GLP-1RA and SGLT2i, in particular, were less likely to be started by patients most likely to benefit from them. GLP-1RA initiation was less likely among patients with prior hypoglycemia requiring ED/hospital care (OR 0.86 [95% CI 0.79-0.93]), myocardial infarction (MI; OR 0.93 [0.89-0.97], or stroke (OR 0.88 [0.85-0.91]), though more likely with nephropathy (OR 1.20 [1.17-1.23]). SGLT2i initiation was less likely with prior hypoglycemia (OR 0.81 [0.73-0.89]), nephropathy (OR 0.80 [0.78-0.0.82]), or heart failure (HF; OR 0.85 [0.82-0.87]). However, DPP-4i initiation was more likely with prior hypoglycemia (OR 1.49 [1.41-1.57]), MI (OR 1.09 [1.05-1.12]), stroke (OR 1.09 [1.06-1.11), HF (OR 1.12 [1.09-1.14]), and nephropathy (OR 1.40 [1.37-1.43]).

Our results do not explain why these drugs are not preferentially used in guideline-recommended contexts, but do highlight missed opportunities to reduce the morbidity and mortality associated with hypoglycemia, cardiovascular disease, and kidney disease in highest risk patients.

Disclosure

R.G. McCoy: None. H. Van Houten: None. J. Ross: Research Support; Self; Centers for Medicare and Medicaid Services, Janssen Pharmaceuticals, Inc., U.S. Food and Drug Administration. P. Karaca-Mandic: None. V.M. Montori: None. N. Shah: None.

Funding

National Institutes of Health (K23DK114497); Agency for Healthcare Research and Quality (1U19HS024075, R01HS025164)

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