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GLP-1 Analogs, Appetite and Satiety

Cierra Harden PharmD Candidate 2013 LECOM School of Pharmacy, Bradenton

Obesity is a major risk factor for the development of diabetes as well as predisposing individuals to hypertension and dyslipidemia.

In the United States, 54.8% of persons with diabetes are obese, and 85.2% are overweight or obese1. All of these conditions when combined together increase a person’s risk for cardiovascular disease which is one of the leading causes of morbidity and mortality in type 2 diabetes2. Many of these patients with multiple comorbidities often have trouble reaching their physician’s prescribed treatment goals. While lifestyle modifications are still the gold standard they often seem unattainable and unrealistic to the obese and overweight patient. It has been well documented that weight control can help improve insulin sensitivity and help restore beta-cell function. The use of GLP-1 analogs in therapeutic regimens may help T2DM patients reach their goals faster and easier.

See more GLP-1 Agonist Resources.

The endogenous incretin hormone glucagon-like peptide 1, GLP-1, is secreted rapidly after the ingestion of nutrients. Biological effects of GLP-1 include glucose dependent insulinotropic effects on the pancreatic beta cells and inhibition of gastric emptying3. Delayed gastric emptying limits food intake, stimulates insulin, and inhibits glucagon secretion after a meal. In diabetic patients this action may reduce postprandial hypoglycemia and may result in weight loss4. It is because of this effect of gastric emptying that it has been proposed that GLP-1 may play a role in appetite and calorie control in humans3.

The following randomized double blind crossover study looked at the effects on appetite suppression and calorie control in twelve males who had been diagnosed with T2DM for at least one year. The mean age of the patients was 55 ± 2 yr; their mean HbA1C was 8.1 ± 0.4, and their mean body mass index was 29.4 ± 1.23. Seven of the patients were on oral antidiabetics and 5 were on diet alone. The subjects were tested on 2 different test days that were separated by at least one week but no more than three weeks. Each subject was instructed to fast overnight and received a standardized fixed calorie breakfast and given an allotted time within which to complete the meal. Later in the day depending on the group they were given an infusion (either GLP-1 at a dose of 1.5 pmol kg-1 min-1 or saline) over the next two hours3. Following the infusion the subjects were invited to lunch where they were invited to eat and drink until completely full. Beginning with the infusion, throughout the meal, and following the meal the subjects were asked to rank their feelings of hunger, fullness, and perceived food consumption every 15 minutes using a visual analog scale of 0-10. To ensure the subjects did not know how much they were consuming all foods and beverages were served in excess and then measured following meal completion. Before each meal and during regular intervals blood samples were taken to measure glucose and hormone levels. Table 1 below shows that the subjects who received the infusion of GLP-1 significantly consumed fewer calories (27%) than those who received the placebo3. None of the subjects reported any major adverse effects from the GLP-1 infusions. Figure 1 below shows how the infusion of GLP-1 affected the VAS scores3. Those who had received the infusion of GLP-1 had a feeling of being full and less hungry before the meal as compared to those who received the placebo.

SE-Lifestyle_Art3-1SE-Lifestyle-Art3-2 3

The above study indicates that the hormone GLP-1 may prove to be beneficial in helping to curb a patient’s appetite or promote a feeling of fullness. Currently the main use of GLP-1 analogs is in the prevention of hyperglycemia associated with T2DM. However, GLP-1 analogs’ other benefits currently being studied, including the promotion of satiety, could help patients succeed in making the lifestyle changes so critical to their health.

  1. Prevalence of overweight and obesity among adults with diagnosed diabetes – United States, 1988-1994 and 1999-2002. MMWR Morb Mortal Wkly Rep2004; 53: 1066–1068
  2. Niswender, K.(2010) Diabetes and obesity: therapeutic targeting and risk reduction – a complex interplay. Diabetes, Obesity and Metabolism, 12: 267-287. Doi:10.1111/j.1463-1326.2009.01175.x
  3. Gutzwiller, J. Drewe, J. et.al. Glucagon-like peptide-1 promotes satiety and reduces food intake in pateints with diabetes mellitus type 2. Am J Physiol Regul Integr Comp Physiol. 1999; 276: R1541-1544.
  4. Glucagon like peptide. (n.d.). Retrieved from http://www.obesity101.com/101-3.htm
  5. Garber, A. Incretin-Based Therapies in the Management of Type 2 Diabetes: Rationale and Reality in a Managed Care Setting. The American Journal of Managed Care. 2010; 16(supp7):S187-194.

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