Diabetes Mellitus
Manual of Clinical Nutrition Management III- 30 Copyright © 2013 Compass Group, Inc.
reduced risk of hypoglycemia (2). Nonsulfonylureas are an option for patients who have erratic meal
schedules and are concerned about weight gain (2).
Insulin sensitizers (biguanides, thiazolidinediones, and -glucosidase inhibitors): These drugs enhance
insulin action. To be effective, these drugs require the presence of endogenous or exogenous insulin.
Biguanides provide enhanced insulin sensitivity by inhibiting hepatic gluconeogenesis and, to a lesser
extent, glycogenolysis. Metformin, the only biguanide, causes weight loss and does not cause hypoglycemia
when it is used as a monotherapy (2). Metformin can cause gastrointestinal side-effects such as abdominal
pain, nausea, diarrhea, and metallic taste. Starting with small doses of medication and limiting foods such as
cauliflower, cabbage, broccoli, lentils, and legumes may lessen these side effects (2). Patients who have
compromised renal function or who are at risk for dehydration or chronic heart failure should be closely
monitored for the risk of lactic acidosis associated metformin (2).
Thiazolidinediones enhance insulin sensitivity by increasing the efficiency of the glucose transporters.
Thiazolidinediones, particularly pioglitazone, beneficially affect lipids by decreasing triglyceride levels,
increasing the high-density lipoprotein cholesterol level, and increasing the particle size of low-density
lipoprotein cholesterol (2). The main side effects of thiazolidinediones are weight gain and mild edema;
therefore, an energy-controlled diet and sodium modification may be warranted (2).
The -glucosidase inhibitors inhibit enzymes that digest carbohydrates in the small intestine. This
inhibition results in delayed carbohydrate absorption and lowered postprandial glucose responses. The -
glucosidase inhibitors should be taken before carbohydrate-containing meals or snacks and should not be
taken when meals are missed (2). These medications should be avoided by persons who have severe renal or
hepatic impairment or any gastrointestinal disease. The side effects of -glucosidase inhibitors include
bloating, abdominal cramps, flatulence, and diarrhea (2).
Dipeptidyl peptidase IV inhibitors: These drugs inhibit dipeptidyl peptidase IV, the enzyme that degrades
endogenously secreted incretins (2). Because of this mechanism, increased levels of incretin hormones result
in increased insulin secretion. The most common side effects are headaches and nasopharyngitis (2).
Sitagliptin, the first dipeptidyl peptidase inhibitor IV approved for use as a monotherapy or in combination
with a thiazolidinedione or metformin, is metabolized in the liver but excreted in the urine. In patients with
renal insufficiency, the dose should be decreased by 50% to 75% (2).
Incretin mimetics: These drugs mimic the glucose-lowering effects of the incretin hormone, a glucagon-like
peptide that occurs naturally in the body. Exenatide (Byetta) represents a new class of injectable medications
for people with type 2 diabetes who take metformin or sulfonylurea agents. Exenatide is an amino-acid
peptide that has many of the glucose-lowering effects of incretin (1,3). The glucose-lowering effects of this
drug result from a delay in gastric emptying and enhanced glucose-dependent insulin secretion from the beta
cells. But, these effects occur only in the presence of elevated glucose levels and decreased insulin production
(3). Exenatide is usually injected twice a day, at breakfast and the evening meal. It can be taken up to 60
minutes before a meal, but taking the medication 30 or more minutes prior to a meal may increase the sense
of satiety early in the meal, resulting in decreased energy intake (1,3). Because the mechanism slows gastric
emptying, a feeling of fullness may be experienced during meals and can cause nausea or early satiety (2).
Exenatide is associated with a degree of weight loss over a 2-year period (3).
Amylinomimetics: These drugs counter the effects of amylin deficiency. Amylin is a hormone secreted with
insulin by the pancreatic beta cells in response to food intake. Amylin lowers glucose levels by slowing
gastric emptying and decreasing postprandial hepatic glucose release, which is related to a decrease in
glucagon production from the pancreatic alpha cells and is dependent on the glucose level (2,3). Pramlintide
(Symlin), an injectable drug, is a form of amylin. Pramlintide is approved as an adjunct therapy to insulin
therapy in patients who have type 1 or type 2 diabetes and have not achieved optimal glucose control (3).
Pramlintide, which must be injected separately from insulin, should be given with each meal or snack that
exceeds 250 kcal of energy or 30 g of carbohydrate (3).