New drug may be 'next big thing' in type 2 diabetes management

The Bottom Line

  • Type 2 diabetes is a chronic but common condition that usually requires medication to keep blood sugar levels stable.
  • Issues and side effects of some oral hypoglycemic agents (such as glyburide) and insulin use include low blood sugar (hypoglycemia) which can be dangerous and also can lead to weight gain.
  • Newer injectable drugs (GLP-1 agonists) used in combination with older oral hypoglycemic agents or insulin can help people with type 2 diabetes avoid low blood sugar and weight gain.
  • Injectable GLP-1 agonists taken weekly (such as exenatide-long-acting-release, dulaglutide, and taspoglutide) may be more effective for blood sugar control than some GLP-1 agonists that need to be taken more frequently.  

Diabetes is a very common chronic disease which is challenging to manage. In Canada, about 90% of people with this condition have type 2 diabetes, which occurs when the body does not effectively make, release or use insulin (1). Insulin is a hormone that helps the body convert sugar into energy. For people with type 2 diabetes, sugar can quickly build up in the blood and cause hyperglycemia (high blood sugar) which can lead to serious health problems, even death (1).


While changes in diet and physical activity are the first strategies used to manage type 2 diabetes, many people also use medication – “oral hypoglycemic agents” (such as metformin) or insulin – to help control their blood sugar levels. People who take insulin must monitor their blood sugar levels regularly and give themselves injections of insulin, often several times a day, as instructed by their health care providers.


For many people with diabetes, taking insulin is a vital part of their self-care routine. However it’s not without its shortcomings. For example if insulin levels are not carefully balanced with diet, people can experience hypoglycemia (low blood sugar) and weight gain (2).


That’s why a relatively new type of injectable drug is getting a lot of attention. Glucagon-like peptide-1 (GLP-1) agonists (such as exenitide and liraglutide) work by mimicking the functions of certain hormones in the body that help lower blood sugar levels after eating (3). In theory, when used in combination with insulin, GLP-1 agonists should not only offer better blood sugar control but also reduce the risk of both low blood sugar and weight gain, or even actually help lower weight. It sounds good, but is it too good to be true?


A systematic review examined the results of 15 studies – all randomized controlled trials. More than 4,300 men and women with type 2 diabetes were prescribed either GLP-1 agonists with insulin or another diabetic treatment – generally insulin alone. Participants’ blood sugar levels and weight were measured over at least 12 weeks of this treatment (4).


What the research tells us

Compared with other treatments for diabetes, GLP-1 agonists – combined with insulin – consistently and significantly improved blood sugar levels without increasing the risk of low blood sugar. And not only did the drugs prevent further weight gain, they actually contributed to weight loss (4).


This is a promising finding, because if blood sugar can be controlled more effectively, and if low blood sugar and weight gain are no longer among the frustrations associated with the condition, diabetes management may become easier for millions of people.


More recently, newer versions of GLP-1 agonists have become available that only need to be taken once a week (such as exenatide-long-acting-release, dulaglutide, and taspoglutide). Research shows that these weekly medications might be more effective in controlling blood sugar levels than some GLP-1 agonists that have to be taken more frequently, while causing similar weight loss and side effects (5).


The evidence behind GLP-1 agonists, regardless of the frequency that they need to be taken, has been highly encouraging. Further research will need to address questions about the long-term effectiveness, safety, and side effects of GLP-1 agonists.


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References

  1. Public Health Agency of Canada.  Diabetes in Canada: Facts and figures from a public health perspective. [Internet] 2011. [cited July 2015]. Available from http://www.phac-aspc.gc.ca/cd-mc/publications/diabetes-diabete/facts-figures-faits-chiffres-2011/pdf/facts-figures-faits-chiffres-eng.pdf 
  2. Russel-Jones D, Khan R. Insulin-associated weight gain in diabetes – causes, effects and coping strategies. Diabetes Obes Metab. 2007; 9: 799-812. doi: 10.1111/j.1463-1326.2006.00686.x.
  3. Vilsbol T, Christensen M, Junker et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: Systematic review and meta-analysis of randomised controlled trials. BMJ. 2012; 344:d7771. 
  4. Eng C, Kramer C, Zinman B, et al. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: A systematic review and meta-analysis. Lancet. 2014; 384:2228-34. doi: 10.1016/S0140-6736(14)61335-0.  
  5. Xue X, Ren Z, Zhang A, et al. Efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists compared with exenatide and liraglutide in type 2 diabetes: a systemic review of randomised controlled trials. Int KJ Clin Pract. 2016; 70(8):649-656. doi: 10.1111/ijcp.12847. 

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