Is glucagon-like peptide-1 analogue therapy helpful in type 1 diabetes?

The results of the study by Frandsen and colleagues (summarised alongside) are essentially negative, but the study may still be helpful. Over the past few years, new therapies have transformed the treatment of type 2 diabetes. New classes of medications have allowed us to control blood glucose with a reduced risk of hypoglycaemia and weight gain. For some patient groups, hypoglycaemia represents a high clinical risk. Weight gain is likely to translate into increased cardiovascular risk; it therefore follows that reduced weight gain is likely to translate into reduced cardiovascular risk – although we await definitive studies showing this.

Glucagon-like peptide-1 (GLP-1) receptor agonist therapy has proven to be one of the more powerful tools we have in type 2 diabetes. The longer-term studies that have now been published suggest that GLP-1 analogue therapy, alone or in combination with insulin, results in improved glucose control and reduced weight gain over time when compared with insulin therapy alone. Defining the specific group of people with type 2 diabetes who will benefit most is more difficult. Taking this further, the evidence that GLP-1 analogues may benefit individuals with type 1 diabetes is even more tenuous.

It is perhaps worth considering why we might want to consider using GLP-1 analogues in type 1 diabetes. What could be the possible benefits? This class of medications have undoubted benefits in reducing weight gain and have been shown to reduce insulin dose requirements in overweight, insulin-resistant subjects. We might, therefore, want to study a group of overweight individuals with type 1 diabetes and high insulin requirements.

One of the key features of type 2 diabetes is dysregulation of glucagon secretion, with overproduction of glucagon after meals. Frandsen and colleagues suggest that this is also a problem in type 1 diabetes, but actually the evidence for this is not clear. There is a strong suggestion that glucagon secretion is, in fact, downregulated in long-standing type 1 diabetes (although the evidence mostly relates to hypoglycaemia). The study population here comprised normal-weight individuals, and glucagon secretion was not measured. Although the overall conclusion was that there was no major benefit in this patient group, this does not rule out the possibility that GLP-1 analogues may help a subgroup of people with type 1 diabetes.

To read the article summaries, please download the PDF