Does CKD modify the effects of GLP-1RA and SGLT2i on weight loss?

Background: It is unknown whether CKD modifies the weight loss effects of GLP1-RA or SGLT2i.

Methods: In an active comparator, new user study, we examined the effects of CKD status on bodyweight loss in veterans with T2D on metformin who began insulin glargine (IG), SGLT2i, or GLP1-RA from 1/1/18 to 3/31/21. Previous use of study medications between 1/1/08 and 12/31/17 was an exclusion. Index date was the date of study drug prescription fill. Outpatient bodyweight closest to the index date and within 1 year prior was defined as baseline bodyweight. Bodyweight change after drug initiation was defined as the difference between baseline bodyweight and an average of all outpatient weights across 6-month intervals after the index date, up to 24 months.

Follow up was until 24 months after index date or until loss to follow-up or death, whichever came earliest. Inverse probability weights (IPW) for each pairwise drug comparison resulted in balance of baseline variables across the drug classes. In IPW mixed effects models, study drug classes were related to weight change at 24 months in pairwise comparisons in non-CKD and CKD (eGFR<60) subgroups. Effect modification was tested by comparing the regression coefficients for each of the pairwise comparisons in non-CKD and CKD subgroups.

Results: In the non-CKD group (N = 124,963), the percentages of female patients for GLP1-RA, SGLT2i, and IG respectively were 9.7%, 4.4%, and 5.9%. Mean ages were 62, 65, and 63; baseline eGFRs were 87.3, 85.6, and 87.3; and baseline BMIs were 35.8, 33.4, and 32.6, respectively. In the CKD group (N = 25,124), the percentages of female patients for GLP1-RA, SGLT2i, and IG respectively were 6.1%, 3.4%, and 4.3%. Mean ages were 71, 72, and 71; baseline eGFRs were 48.7, 51.0, and 48.6; and baseline BMIs were 34.2, 32.2, and 31.8, respectively.

Absolute bodyweight difference at 24 months for IG compared to GLP1-RA was 6.77 ± 0.22 lbs in the non-CKD group and 7.15 ± 0.48 lbs in the CKD group (interaction p-value = 0.476). Corresponding numbers for IG compared to SGLT2i were 6.13 ± 0.18 lbs and 6.18 ± 0.37 lbs (interaction p-value = 0.906) and SGLT2i compared to GLP1-RA were 0.64 ± 0.20 and 0.97 ± 0.45 (interaction p-value = 0.507). Percent bodyweight difference at 24 months for IG compared to GLP1-RA was 3.01 ± 0.10 in the non-CKD group and 3.31 ± 0.21 in the CKD group (interaction p-value = 0.219). Corresponding numbers for IG compared to SGLT2i were 2.75 ± 0.08 and 2.92 ± 0.17 (interaction p-value = 0.365) and SGLT2i compared to GLP1-RA were 0.26 ± 0.09 and 0.39 ± 0.21 (interaction p-value = 0.575).

Conclusion: Patients lost significantly more weight on GLP1-RA or SGLT2i compared to insulin glargine, but there was minimal difference in weight change at 2 years between SGLT2i and GLP1-RA. CKD status did not modify weight loss on SGLT2i or GLP1-RA.