SUN-648 - Evaluating Factors Associated with A Favorable Response to A Combination of SGLT2 Inhibitors and GLP-1 Receptor Agonists Versus Either Agent Alone in Patients with Type 2 Diabetes Mellitus (T2DM) in Veterans Affairs Health Care System

Background
The global prevalence of T2DM is approximately 537 million and is projected to reach 783 million by 2045(1). SGLT2 inhibitors (SGLT2i) and GLP –1 receptor agonist (GLP-1RA) are now recommended as the first line agents for treatment of T2DM. However, clinical experience has shown variable response to these agents either alone or when combined together in approximately 40% of the population (2).

AIMS
We evaluated the decrease in HbA1c and weight in veterans with T2DM on a combination of both GLP-1 RA and SGLT2i vs either agent alone and factors which predicted a favorable response to treatment.

Methodology
Retrospective analysis of veterans aged 18 – 89 years with T2DM between January 2015 till July 31, 2020, was done who were initiated on either an SGLT2i and GLP-1RA or both and were on the combination for at least 6 months. The two main outcomes were defined as: a decrease in baseline HbA1c of at least 0.5 % and a decrease in weight in pounds of at least 3% from baseline within 6 months after being on both the agents. The outcome variable was either having a complete response (both weight and HbA1c responses) or not. Associations with having a complete response were assessed using Chi-square and independent samples t-tests, and adjusted odds ratios of having a complete response were generated from a logistic regression.

Results
741 patients were included and 134 (18.1%) of them were on the combination for at least 6 months. The sample was primarily male (92.2%), White (89.1%) with mean age of 68.1 years. The mean HbA1c was 8.5 ±1.39 with 471(63.6%) of the people having HbA1c >8 %.
Overall, 202 (24.3%) of patients in the sample had a reduction of both HbA1c and weight. There was a significant difference in patients who had a complete response based on medication group: GLP-1RA (34.0%), SGLT2i (19.6%), and combo therapy (26.1%), p < 0.001.
When adjusting for potential confounders (i.e., age, sex, race, and baseline HbA2c, BMI, blood pressure, insulin use, and metformin use), a significant association remained between medication group and having a complete response, p = 0.02; GLP-1RA alone was associated with a significantly higher odds of having a complete response (AOR = 1.94 (95% CI: 1.10, 3.41)), but the combination of GLP1 and SGL2 was not (AOR = 1.49 (95% CI: 0.78, 2.85)), relative to SGLT2i alone. Other variables significantly associated with having a complete response in the model included older age and higher baseline HbA1c.

Conclusion
Older patients and those with a higher HbA1c at baseline had a are likely to have a complete response within the first 6 months. Using a combination of SGLT2i and GLP-1RA was not associated with having a higher odds of experiencing both a reduction of weight and/or HbA1c compared to using either alone likely due to the fact that patients on the combination were not on the higher doses of GLP-1RA, but GLP-1RA only users had a significantly higher odds of having a response than patients on SGLT2i.

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