Diabetics may try a variety of medications and lifestyle changes before finding the combination that works best. A new study finds that third-line treatments may do the trick when first- and second-line drugs – like metformin and sulphonylureas – aren’t enough. Since most third-line drugs are equally effective, the side effect profile of the treatments may make the choice of which drug to add more clear.

The researchers behind the current study wondered how these medications compared, in effectiveness and in side-effects.

Metformin is usually considered the first-line treatment for blood sugar control, but according to a new study, its effects often "deteriorate" in the first few years. At this point, doctors turn to the second-line treatment, sulphonylureas, which may help initially, but again the effects can fall off in the first six months.

The third-line medications, which include insulin, thiazolidinediones, glucagon-like peptide-1 (GLP-1) agonists, α-glucosidase inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors, are sometimes prescribed. The researchers behind the current study wondered how these medications compared, in effectiveness and in side-effects.

The new study followed over 4,500 diabetic participants, who were on metformin and sulphonylureas, for an average of 31 weeks. Patients were placed one of the third-line medications mentioned above. The team tracked the participants’ hemoglobin AC1 (HbA1C) levels, which gives an estimate of blood sugar over the long term (2-3 months). They also looked at the patients’ weight gain or loss, and their likelihood of suffering major hypoglycemic (low blood sugar) episodes, which can result from diabetes medication and be risky under certain circumstances.

All of the third-line treatments led to similar reductions in the participants’ HbA1C levels. There was more weight gain with insulin (about 6 pounds) and the thiazolidinediones (about 9 pounds), compared to the other medications. Insulin also cause about twice the number of significant hypoglycemic episodes as the other medications. Patients on GLP-1 agonists lost about 3.6 pounds.

It’s important to note that the study was a relatively short-term analysis (31 weeks); future research will need to compare the medications over the longer term to determine how the medications measure up over years or decades.

Since the effects on blood sugar were about the same with all of the third-line medications, taking the side-effects into account when choosing a treatment may be the way to go. Those who are overweight may want to stay away from insulin and thiazolidinediones, for example. It is important to have a good discussion with your doctor about the pros and cons associated with each medication, so that you can arrive at the best decision for your specific needs.

The study, carried out by a team at the Hospital de Clinicas de Porto Alegre in Brazil, was published in the May 17, 2011 issue of Annals of Internal Medicine.