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. 2024 Dec;29(4):406-414.
doi: 10.1111/jns.12664. Epub 2024 Oct 22.

Glucose-lowering medication associated with weight loss may limit the progression of diabetic neuropathy in type 2 diabetes

Georgios Ponirakis  1 , Ibrahim Al-Janahi  2 , Einas Elgassim  1 , Rawan Hussein  1 , Ioannis N Petropoulos  1 , Hoda Gad  1 , Adnan Khan  1 , Hadeel B Zaghloul  1 , Mashhood A Siddique  2 , Hamda Ali  2 , Fatima F S Mohamed  1 , Lina H M Ahmed  1 , Youssra Dakroury  1 , Abeer M M El Shewehy  1 , Ruba Saeid  1 , Fadwa Mahjoub  1 , Shaikha N Al-Thani  1 , Farheen Ahmed  1 , Moayad Homssi  1 , Salah Mahmoud  1 , Nebras H Hadid  1 , Aisha Al Obaidan  1 , Iuliia Salivon  2 , Ziyad R Mahfoud  1 , Mahmoud A Zirie  2 , Yousuf Al-Ansari  2 , Stephen L Atkin  3 , Rayaz A Malik  1   4   5
Affiliations

Glucose-lowering medication associated with weight loss may limit the progression of diabetic neuropathy in type 2 diabetes

Georgios Ponirakis et al. J Peripher Nerv Syst. 2024 Dec.

Abstract

Aim: Obesity is a major risk factor for diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2D). This study investigated the effect of glucose lowering medication associated with weight change on DPN.

Methods: Participants with T2D were grouped based on whether their glucose lowering medications were associated with weight gain (WG) or weight loss (WL). They underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function and corneal confocal microscopy (CCM) at baseline and follow-up between 4 and 7 years.

Results: Of 76 participants, 69.7% were on glucose lowering medication associated with WG, and 30.3% were on glucose lowering medication associated with WL. At baseline, participants in the WG group had a significantly longer duration of diabetes (p < .01), higher douleur neuropathique en 4 (DN4) score (p < .0001) and VPT (p = .01) compared with those in the WL group. Over a 56-month period, participants in the WG group showed no significant change in body weight (p = .11), HbA1c (p = .18), triglycerides (p = .42), DN4 (p = .11), VPT (p = .15) or Sudoscan (p = .43), but showed a decline in corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) (p < .0001). Participants in the WL group showed a reduction in weight (p = .01) and triglycerides (p < .05), no change in DN4 (p = .30), VPT (p = .31) or Sudoscan (p = .17) and a decline in the corneal nerve branch density (p < .01).

Conclusions: Participants treated with glucose lowering medication associated with weight gain had worse neuropathy and greater loss of corneal nerves during follow-up, compared to patients treated with medication associated with weight loss.

Keywords: corneal confocal microscopy; diabetic peripheral neuropathy; glucose lowering medication; type 2 diabetes; weight change.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Corneal confocal microscopy images and CNFL changes over 6 years in participants with type 2 diabetes on glucose lowering medications associated with weight loss or weight gain. Images of corneal nerve fibers (yellow arrows) in a participant treated with medications associated with weight loss (WL) at baseline (A) and at 6‐year follow‐up (B) and in a participant treated with medication associated with weight gain (WG) at baseline (C) and at 6‐year follow‐up (D) demonstrating a reduction in nerve fibers at follow‐up. The accompanying line graph compares change in corneal nerve fiber length (CNFL) from baseline to year 6 in participants on WL medications (black line) and WG medications (red line), demonstrating a greater reduction in the WG group.
See this image and copyright information in PMC

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