ADA 2010

In a session discussing the management of insulin resistant people with type-2 diabetes treated with insulin Professor Matthew Riddle reviewed current knowledge of this patient group.

He reminded delegates of the recent publication of the 4-T study (Holman RR et al. NEJM 2009; 361: 1736-47) in which it was demonstrated that even with intensive treatment algorithms about 50% of insulin treated type-2 diabetic patients do not achieve a HbA1c < 7.0%.

He pointed out that attainment of this target is affected by HbA1c at initiation of insulin therapy with fewer patients achieving target if HbA1c is > 8.5% at introduction of injections (Riddle MC et al. Diabetes 2009; 58 (suppl 1) A125).

Data exist which show that attainment of ideal target morning fasting glucose by bedtime basal insulin is possible. However the addition of prandial insulin often fails to maintain post-meal normoglycaemia, and the result is that pre-meal glucose values do not return to target. Furthermore, insulin use in type-2 diabetes is associated with both weight gain and hypoglycaemia.

Thus the hunt is on for a therapy, or combination of therapies which will attain targets in greater numbers, ideally lead to less hypoglycaemia and attenuate weight gain in this already insulin resistant group of patients.

Professor Riddle went on to present some recent data from the INSTEAD study (Riddle MC. Diab Care 2009; 32: 1577-82) which suggest that combining the Amylin analogue Pramlinitide to basal insulin results in less insulin use, equivalent HbA1c reduction and zero hypoglycaemia when compared to the addition of prandial insulin.

He then showed data presented in late breaking abstracts at this year’s ADA meeting which suggest that combining the GLP-1 analogue Exenatide with glargine insulin results in statistically more patients achieving an HbA1c target < 7.0% in the MEXELIN study (Riddle MC et al. 18-LB ADA2010). This exciting data are extended by the observation that adding exenatide to insulin glargine achieved glycaemic targets whilst achieving weight loss and without increased risk of hypoglycaemia (Buse et al. 10-LB ADA 2010).

Whilst we await the publication of ongoing longer term outcome studies investigating the combination of insulin and GLP-1 analogues, these data suggest that there may be efficacy and safety reasons for clinical use of such combinations in overweight insulin resistant patients.