Weight management in diabetes: study highlights neuroprotective role of weight loss medications

Aims: To evaluate the impact of glucose-lowering medications, distinguished by their association with weight gain (WG) or weight loss (WL), on diabetic peripheral neuropathy (DPN) outcomes in individuals with type 2 diabetes (T2D).

Methods: This observational study included 76 participants with T2D, stratified by their glucose-lowering medications: WG group (e.g., insulin, sulfonylureas, thiazolidinediones) versus WL group (e.g., metformin, GLP-1 receptor agonists, SGLT2 inhibitors). The study is a continuation of a 2-year follow-up study investigating physical activity and glucose lowering medications conducted at the National Diabetes Center in Hamad General Hospital in Qatar. Over a 4–7-year follow-up period, participants underwent clinical and metabolic assessments, including evaluations of neuropathic symptoms using DN4 scores, corneal confocal microscopy (CCM), vibration perception threshold (VPT), and sudomotor function.

Results: At baseline, the WG group exhibited more severe neuropathic symptoms, reflected in higher VPT and DN4 scores, compared to the WL group. Follow-up assessments revealed a greater reduction in body weight (-6.7±11.7 vs -3.3±14.6) and triglyceride levels (-0.5±1.1 vs 0.0±1.6), in the WL group compared to the WG group. CCM revealed changes in corneal nerve fiber density (CNFD, 0.2±7.4 vs -5.2±6.9), nerve branch density (CNBD, -18.9±28.5 vs -27.7±6.4), and nerve fiber length (CNFL, -0.4±4.8 vs -3.5±4.7) in the WL and WG groups, respectively. For the WL group these findings indicate stable CNFD and CNFL measures with a slight decline in CNBD. No changes were observed in VPT, DN4, and sudomotor function from baseline to follow-up in either group.

Conclusions: This study shows an association between glucose-lowering medications and DPN progression in T2D, demonstrating that WG-related treatments may contribute to neuropathic decline, while WL medications show a potential neuroprotective effect.

Comments. Patients on WL medications exhibited stable corneal nerve fiber metrics, while those on WG medications showed nerve degeneration. Although this study provides valuable insights, its small observational design limits the generalizability of the findings. Additionally, differences in basal diabetes duration and neuropathy severity, and potential differences in socioeconomic status between the WG and WL groups - related to different medication costs - may have influenced the results. To fully understand the long-term effects of WL medications on DPN, a multicenter, randomized controlled trial with extended follow-up is needed to determine whether improvements extend to other measures of neuropathy. Further investigations into the potential mechanisms by which WL medications exert neuroprotective effects, and differences among WL medications would be of interest. This study highlights the significant role of weight management in diabetes care, showing that WL medications may protect against DPN in T2D. The findings align with the American Diabetes Association's recommendation to prioritize weight-neutral and weight loss inducing medications in T2D management, emphasizing the dual benefits of WL medications in metabolic control and DPN prevention.

Mette Krabsmark Borbjerg

Reference. Ponirakis G, Al-Janahi I, Elgassim E, Hussein R, Petropoulos IN, Gad H, Khan A, Zaghloul HB, Siddique MA, Ali H, Mohamed FFS, Ahmed LHM, Dakroury Y, El Shewehy AMM, Saeid R, Mahjoub F, Al-Thani SN, Ahmed F, Homssi M, Mahmoud S, Hadid NH, Obaidan AA, Salivon I, Mahfoud ZR, Zirie MA, Al-Ansari Y, Atkin SL, Malik RA. Glucose-lowering medication associated with weight loss may limit the progression of diabetic neuropathy in type 2 diabetes. J Peripher Nerv Syst. 2024 Oct 22. doi: 10.1111/jns.12664. Epub ahead of print. PMID: 39439079.

https://onlinelibrary.wiley.com/doi/10.1111/jns.12664