Effect Of Diabetes Medications On Weight Loss

Diabetes has been a continually growing concern in the United States. More than 100 million U.S. adults are living with diabetes or pre-diabetes based on Centers for Disease Control and Prevention (CDC) 2015 data. Diabetes is manageable through diet, physical activity, and medications. Type 2 Diabetes management should be a patient-centered approach. This includes assessing the patient’s history/background, target goals, and lifestyle to find which medications are best for each patient. 

Weight is a major factor leading to diabetes and an important consideration in the selection of diabetes medications because more than 80% of people with type 2 Diabetes are either overweight or obese.  Here is a review of the effect of diabetes medications on weight loss.

Biguanide

Biguanides decrease glucose production by the liver and reduce intestinal absorption of glucose, therefore resulting in increasing peripheral glucose uptake and consumption. Biguanides also improve glucose use in skeletal muscle and fat tissues by increasing cell membrane glucose transport. An average weight loss of 1 to 8.4 pounds was reported in clinical trials of adults using metformin immediate release tablets as monotherapy. Average weight loss in patients receiving metformin extended-release tablets was 0.7 to 2.2 lbs. Metformin continues to be the optimal drug for monotherapy. Kidney function should be assessed prior to starting. Medication in this class include:

• Glucophage (metformin)

DPP-4 Inhibitors

DPP-4 inhibitors increase the effects of the incretin hormones glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Incretins help the pancreas produce more insulin only when needed and also reduce the amount of glucose produced by the liver. They are not associated with weight changes. They should be used cautiously in patients with preexisting heart failure and history of pancreatitis. Medications in this class include:

• Nesina (alogliptin)
• Onglyza (saxagliptin)
• Tradjenta (linagliptin)
• Januvia (sitagliptin)
• Galvus (vildagliptin)

SGLT2 Inhibitors

SGLT2 inhibitors block the reabsorption of glucose by the kidneys, causing glucose to be excreted in the urine. They are associated with weight loss due to volume depletion from increased urination. Clinical trial data for SGLT2 inhibitors have shown a weight loss of 2.2 to 3.9 kg when used as monotherapy and 2.6 to 4.2 kg when used in combination with metformin. Renal function should be assessed prior to starting these medications. Medications in this class include:

• Invokana (canagliflozin)
• Farxiga (dapagliflozin)
• Jardiance (empagliflozin)

GLP-1 Receptor Agonists

GLP-1 agonists reduce blood glucose by increasing insulin production by the pancreas, slowing the absorption of glucose from the gut, and reducing the activity of glucagon (a hormone that increases the release of glucose from the liver). They are associated with weight loss because they delay emptying of the stomach and increase satiety. Additionally, clinical trials for GLP-1 receptor agonists have shown weight loss of 2.3 to 2.8 kg when used as monotherapy and 2.6 to 2.9 kg weight loss when used in combination with metformin. In fact, a trial for the use of liraglutide for weight loss showed an average of 5.8 kg weight loss compared to an average loss of 3.8 kg in the placebo group after 1 year. Saxenda (liraglutide) is a weight loss medication approved by the FDA.  Medication in this class include:

• Tanzeum (albiglutide)
• Trulicity (dulaglutide)
• Byetta, Bydureon (exenatide)
• Victoza, Saxenda (liraglutide)
• Adlyxin (lixisenatide)

Of course, weight is not the only concerning factor for diabetes management. These medications should not be given without regard to hypoglycemic risks, side effects, costs, and other co-morbidities including but not limited to coronary artery disease, heart failure, renal and liver disease and dementia.

References and Resources:

ADA Diabetes Care 2012: Management of Hyperglycemia in Type 2 Diabetes

ADA Diabetes Care 2015: Management of Hyperglycemia in Type 2 Diabetes

Centers of Disease Control and Prevention

Farxiga Package Insert

Invokana Prescribing Information

Jardiance Prescribing Information

Astrup et al. (2012). Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. International Journal of Obesity. 36: 843-854.