Effect of treatment with exenatide and pioglitazone or basal-bolus insulin on diabetic neuropathy: A substudy of the Qatar Study

Georgios Ponirakis, Georgios Ponirakis, Muhammad A. Abdul-Ghani, Amin Jayyousi, Hamad Almuhannadi, Ioannis N. Petropoulos, Adnan Khan, Hoda Gad, Osama Migahid, Ayman Megahed, Ralph Defronzo, Ziyad Mahfoud, Mona Hassan, Hanadi Al Hamad, Marwan Ramadan, Uazman Alam

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2 Scopus citations

Abstract

Introduction To assess the effect of exenatide and pioglitazone or basal-bolus insulin on diabetic peripheral neuropathy (DPN) in patients with poorly controlled type 2 diabetes (T2D). Research design and methods This is a substudy of the Qatar Study, an open-label, randomized controlled trial. 38 subjects with poorly controlled T2D were studied at baseline and 1-year follow-up and 18 control subjects were assessed at baseline only. A combination of exenatide (2 mg/week) and pioglitazone (30 mg/day) or glargine with aspart insulin were randomly assigned to patients to achieve an HbA1c <53 mmol/mol (<7%). DPN was assessed with corneal confocal microscopy (CCM), DN4, vibration perception and sudomotor function. Results Subjects with T2D had reduced corneal nerves, but other DPN measures were comparable with the control group. In the combination treatment arm (n=21), HbA1c decreased by 35.2 mmol/mol (3.8 %) (p<0.0001), body weight increased by 5.6 kg (p<0.0001), corneal nerve branch density increased (p<0.05), vibration perception worsened (p<0.05), and DN4 and sudomotor function showed no change. In the insulin treatment arm, HbA1c decreased by 28.7 mmol/mol (2.7 %) (p<0.0001), body weight increased by 4.6 kg (p<0.01), corneal nerve branch density and fiber length increased (p≤0.01), vibration perception improved (p<0.01), and DN4 and sudomotor function showed no change. There was no association between the change in CCM measures with change in HbA1c, weight or lipids. Conclusions Treatment with exenatide and pioglitazone or basal-bolus insulin results in corneal nerve regeneration, but no change in neuropathic symptoms or sudomotor function over 1 year.

Original languageEnglish (US)
Article numbere001420
JournalBMJ Open Diabetes Research and Care
Volume8
Issue number1
DOIs
StatePublished - Jun 23 2020

Keywords

  • Glucagon-Like Peptide 1
  • diabetic neuropathies
  • insulin glargine
  • pioglitazone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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    Ponirakis, G., Ponirakis, G., Abdul-Ghani, M. A., Jayyousi, A., Almuhannadi, H., Petropoulos, I. N., Khan, A., Gad, H., Migahid, O., Megahed, A., Defronzo, R., Mahfoud, Z., Hassan, M., Al Hamad, H., Ramadan, M., & Alam, U. (2020). Effect of treatment with exenatide and pioglitazone or basal-bolus insulin on diabetic neuropathy: A substudy of the Qatar Study. BMJ Open Diabetes Research and Care, 8(1), [e001420]. https://doi.org/10.1136/bmjdrc-2020-001420