eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Diabetes Mellitus, Type 2: Treatment & Medication
Updated: Jul 30, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The goal of therapy is to achieve and maintain euglycemia as well as near-normal hemoglobin A1c (HbA1c) levels (£ 7%).
- Patients who are not ill at diagnosis can be treated initially with lifestyle changes (eg, diet, exercise, weight control).
- Because only a few patients can maintain euglycemia with only lifestyle changes, most children and adolescents require medication.
- Insulin therapy is indicated in symptomatic patients with persistent hyperglycemia or with ketoacidosis. After blood glucose levels are controlled, efforts to taper insulin with progressive substitution with an oral agent are undertaken.
- Pharmacologic therapy is indicated when the disease is not well controlled with diet and exercise. Metformin should be the first oral agent used in children and teenagers. If metformin is unsuccessful as monotherapy, the addition of insulin, a sulfonylurea, or another hypoglycemic agent may be appropriate.
Activity
Risk for vascular complications and cardiovascular mortality in patients with diabetes mellitus is increased by poor glucose control. Loimaala et al evaluated the efficacy of a long-term exercise training program on metabolic control and arterial stiffness in patients with type 2 diabetes mellitus. The study showed that long-term endurance and strength training was effective and resulted in improved metabolic control of diabetes mellitus compared with standard treatment; however, significant cardiovascular risk reduction and conduit arterial elasticity did not improve.1
Medication
In general, the treatment of type 2 diabetes in children follows the same rationale as that for treatment in adults. The safety and efficacy of oral hypoglycemic therapy in children and adolescents with type 2 diabetes have not been established; however, physicians have prescribed drugs typically used in adults to treat children and adolescents. Among all the drugs currently in use to treat type 2 diabetes in adults, the US Food and Drug Administration (FDA) has approved only metformin and insulin for use in children.
The FDA has issued an early communication to health care practitioners regarding 4 recently published observational studies that describe the possible association of insulin glargine (Lantus) with an increased risk of cancer.2 Insulin glargine is a long-acting human insulin analogue approved for once-daily dosing.
- The observational studies evaluated large patient databases, and all reported some association between insulin glargine and other insulin products with various types of cancer. The duration of the observational studies was shorter than what is considered necessary to evaluate for drug-related cancers. Additionally, findings were inconsistent within and across the studies, and patient characteristics differed across treatment groups. These issues raise further questions about the actual risk and, therefore, warrants further evaluation.
- The FDA states that patients should not stop taking their insulin without consulting their physician. An ongoing review by the FDA will continue to update the medical community and consumers with additional information as it emerges. Statements from the American Diabetes Association and the European Association for the Study of Diabetes called the findings conflicting and inconclusive and cautioned against overreaction.
Biguanides
These agents reduce hepatic glucose production; they also increase peripheral insulin sensitivity. Metformin rarely induces hypoglycemia. Because of its anorexigenic effects, many treated children maintain or lose weight. Since metformin can lead to ovulatory cycles and resumption of regular menses in patients with PCOS, appropriate counseling should be provided to sexually active adolescents.
Kooy et al found an improved body weight, glycemic control, and insulin requirements when metformin was added to insulin in type 2 diabetes mellitus. No improvement of an aggregate of microvascular and macrovascular morbidity and mortality was observed; however, risk reduction of macrovascular disease was evident after a follow-up period of 4.3 years. Because of these sustained beneficial effects, the policy to continue metformin treatment after the introduction of insulin in type 2 diabetes mellitus should be followed unless contraindicated.3
Metformin (Glucophage)
Use frequently results in weight loss and mild improvement of all aspects of lipid profile. Cannot be used in renal or hepatic insufficiency or decompensated congestive heart failure requiring pharmacologic therapy (increased risk for lactic acidosis). Because of GI adverse effects, titrate slowly and take during (rather than before) meals.
Can be used as monotherapy or with sulfonylureas, glitazones, or insulin. Reduces hepatic glucose output, may decrease intestinal absorption of glucose, and may increase glucose uptake in peripheral tissues. Major drug used in obese patients with type 2 diabetes.
Many patients tolerate metformin best if administered in middle or end of meal. Available as immediate-release (IR) or extended-release (ER) products. Only IR approved for children.
Adult
Initial IR dose: 500 mg PO bid
Maintenance IR dose: 850 mg PO tid
Pediatric
<10 years: Not established
>10 years: Administer as in adults
Diuretics, thyroid products, oral contraceptives, phenytoin, calcium channel blocking drugs, and phenothiazines may decrease effects; cimetidine may increase levels
Documented hypersensitivity; acute myocardial infarction; septicemia; renal disease; decompensated liver disease
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in renal or hepatic insufficiency, decompensated heart failure, and hypoperfusion; discontinue before performing any surgical procedures or procedure involving use of contrast agent
Sulfonylureas
These agents promote insulin release from the pancreas.
Acetohexamide (Dymelor)
Increases insulin secretion from pancreatic beta cells.
Adult
250 mg/d PO qd; may increase by 250-500 mg q5-7d to maximum 1.5 g/d; patients receiving > 1 g may benefit from divided bid dosing
Pediatric
Not established
Clofibrate, fenfluramine, histamine H2 antagonists, androgens, azole antifungals, anticoagulants, chloramphenicol, fluconazole, gemfibrozil, magnesium salts, methyldopa, monoamine oxidase inhibitors (MAOIs), probenecid, salicylates, sulfinpyrazone, urinary acidifiers, and sulfonamides may enhance hypoglycemic effects
Nicotinic acid, oral contraceptives, isoniazid, hydantoins, estrogens, diazoxide, corticosteroids, cholestyramine, beta-blockers, calcium channel blockers, phenothiazines, rifampin, thiazide diuretics, urinary alkalinizers, and sympathomimetics may decrease hypoglycemic effects
May increase effects of digitalis glycosides
Documented hypersensitivity; ketoacidosis; type 1 diabetes mellitus
Pregnancy
D - Unsafe in pregnancy
Precautions
Caution in hepatic and renal impairment; cardiovascular disorders may occur; risk factors include elderly age, malnutrition, irregular eating, impaired renal function, and possibly hepatic dysfunction (if prolonged or recurrent, strongly consider hospital admission); may cause rash, nausea, vomiting, leukopenia, agranulocytosis, aplastic anemia (rare), intrahepatic cholestasis (rare), disulfiram reaction, flushing, headache, nausea, and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) causing hyponatremia
Chlorpropamide (Diabinese)
May increase insulin secretion from pancreatic beta cells.
Adult
100-250 mg PO qd; not to exceed 750 mg/d
Pediatric
Not established
Clofibrate, fenfluramine, histamine H2 antagonists, androgens, azole antifungals, anticoagulants, chloramphenicol, fluconazole, gemfibrozil, magnesium salts, methyldopa, MAOIs, probenecid, salicylates, sulfinpyrazone, urinary acidifiers, and sulfonamides may enhance hypoglycemic effects
Nicotinic acid, oral contraceptives, isoniazid, hydantoins, estrogens, diazoxide, corticosteroids, cholestyramine, beta-blockers, calcium channel blockers, phenothiazines, rifampin, thiazide diuretics, urinary alkalinizers, and sympathomimetics may decrease hypoglycemic effects
May increase effects of digitalis glycosides
Documented hypersensitivity; ketoacidosis; type 1 diabetes mellitus
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in hepatic and renal impairment; cardiovascular disorders may occur
Glipizide (Glucotrol, Glucotrol XR)
Second-generation sulfonylurea that stimulates release of insulin from pancreatic beta cells.
Adult
IR product: 2.5-40 mg/d PO; not to exceed 15-20 mg/dose or 40 mg/d
Pediatric
Not established
Beta-blockers, phenytoin, corticosteroids, and thiazides decrease hypoglycemic effects; cimetidine may increase hypoglycemic effects; angiotensin-converting enzyme (ACE) inhibitors enhance hypoglycemic activity
Documented hypersensitivity; type I diabetes; ketoacidosis
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in renal or liver dysfunction; patients with trauma, infection, surgery, or stress may require insulin
Glyburide (Micronase, DiaBeta, Glynase, PresTab)
Second-generation sulfonylurea. May start at high dose in patients with severe hyperglycemia or those with symptoms, if home glucose monitoring and close follow-up can be arranged.
Adult
5 mg/d PO initially in untreated patients with symptomatic hyperglycemia; not to exceed 20 mg/d PO
Pediatric
Not established
Clofibrate, fenfluramine, histamine H2 antagonists, androgens, azole antifungals, anticoagulants, chloramphenicol, fluconazole, gemfibrozil, magnesium salts, methyldopa, MAOIs, probenecid, salicylates, sulfinpyrazone, urinary acidifiers, and sulfonamides may enhance hypoglycemic effects
Nicotinic acid, oral contraceptives, isoniazid, hydantoins, estrogens, diazoxide, corticosteroids, cholestyramine, beta-blockers, calcium channel blockers, phenothiazines, rifampin, thiazide diuretics, urinary alkalinizers, and sympathomimetics may decrease hypoglycemic effects
May increase effects of digitalis glycosides
Documented hypersensitivity; ketoacidosis; type 1 diabetes mellitus
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in hepatic and renal impairment; cardiovascular disorders may occur; risk factors include elderly age, malnutrition, irregular eating, impaired renal function, and possibly hepatic dysfunction (if prolonged or recurrent, strongly consider hospital admission); may cause rash, nausea, vomiting, leukopenia, agranulocytosis, aplastic anemia (rare), intrahepatic cholestasis (rare), disulfiram reaction, flushing, headache, nausea, and SIADH causing hyponatremia
Tolbutamide (Orinase)
Increases insulin secretion from pancreatic beta cells.
Adult
500-1000 mg PO qd/tid; not to exceed 2 g/d
Pediatric
Not established
Clofibrate, fenfluramine, histamine H2 antagonists, androgens, azole antifungals, anticoagulants, chloramphenicol, fluconazole, gemfibrozil, magnesium salts, methyldopa, MAOIs, probenecid, salicylates, sulfinpyrazone, urinary acidifiers, and sulfonamides may enhance hypoglycemic effects
Nicotinic acid, oral contraceptives, isoniazid, hydantoins, estrogens, diazoxide, corticosteroids, cholestyramine, beta-blockers, calcium channel blockers, phenothiazines, rifampin, thiazide diuretics, urinary alkalinizers, and sympathomimetics may decrease hypoglycemic effects
May increase effects of digitalis glycosides
Documented hypersensitivity; ketoacidosis; type 1 diabetes mellitus
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in hepatic and renal impairment; cardiovascular disorders may occur; risk factors include elderly age, malnutrition, irregular eating, impaired renal function, and possibly hepatic dysfunction (if prolonged or recurrent, strongly consider hospital admission); may cause rash, nausea, vomiting, leukopenia, agranulocytosis, aplastic anemia (rare), intrahepatic cholestasis (rare), disulfiram reaction, flushing, headache, nausea, and SIADH causing hyponatremia
Meglitinides
These agents promote short-term insulin secretion from the pancreas. They are designed to be taken immediately before meals.
Repaglinide (Prandin)
Stimulates insulin release from pancreatic beta cells.
Adult
0.5-4 mg with meals; may dose preprandial bid/qid in response to meal pattern; not to exceed 16 mg/d
Pediatric
Not established
Cytochrome P450 (CYP) 3A4 inhibitors (eg, clarithromycin, ketoconazole, miconazole, and erythromycin) decrease metabolism increasing serum levels and effects; thiazides, diuretics, corticosteroids, estrogens, oral contraceptives, nicotinic acid, calcium channel blockers, phenothiazides, and thyroid products may lead to loss of glycemic control; toxicity is increased with highly protein-bound drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), sulfonamides, anticoagulants, hydantoins, salicylates, and phenylbutazone; increases warfarin effect
Documented hypersensitivity; diabetic ketoacidosis; type 1 diabetes
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in hepatic impairment; if patient exposed to stress, may require insulin therapy because of loss of glycemic control; cardiovascular disorders may occur
Nateglinide (Starlix)
Amino acid derivative that stimulates insulin secretion from pancreas, which in turn reduces blood glucose levels. Action depends on functional beta cells in pancreatic islets. Interacts with ATP-sensitive potassium channel on pancreatic beta cells. Stimulates pancreatic insulin secretion within 20 min of PO administration.
Adult
120 mg PO tid within 30 min ac; may decrease to 60 mg PO tid ac for patients near HbA1c goal
Pediatric
Not established
Metabolized by CYP2C9 (70%) and CYP3A4 (30%); may inhibit CYP2C9; CYP2C9 inhibitors (eg, NSAIDs, fluvoxamine, cimetidine) may decrease elimination; CYP2C9 inducers (eg, carbamazepine, phenobarbital, phenytoin) may enhance elimination; coadministration with NSAIDs, salicylates, MAOIs, and nonselective beta-blocking agents may potentiate hypoglycemic effects; thiazides, corticosteroids, thyroid products, and sympathomimetics may reduce hypoglycemic effects
Documented hypersensitivity; diabetic ketoacidosis
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Reduce dose in hepatic impairment; may cause hypoglycemia; monitor glucose and HbA1C; may cause GI distress
Alpha-glucosidase inhibitors
These agents lower postprandial glucose by slowing glucose absorption; they also delay the hydrolysis of ingested complex carbohydrates and disaccharide. They must be taken immediately before meals.
Acarbose (Precose)
Delays hydrolysis of ingested complex carbohydrates and disaccharides and absorption of glucose. Inhibits metabolism of sucrose to glucose and fructose.
Adult
25 mg PO tid initially with first bite of food at each meal; adjust at 4-8 wk on basis of 1 h postprandial glucose levels and tolerance; uptitrate slowly by 12.5-25 mg/dose; not to exceed maximum of 100 mg tid
Pediatric
Not established
May decrease serum digoxin levels; may increase hypoglycemic effects of sulfonylureas
Documented hypersensitivity; ketoacidosis; cirrhosis; inflammatory bowel disease; colonic ulceration; partial intestinal obstruction or predisposition to intestinal obstruction
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Temporary loss of glucose control seen in stress resulting from fever, trauma, infection, or surgery, which may require temporary insulin therapy
Miglitol (Glyset)
Delays glucose absorption in small intestine and lowers postprandial hyperglycemia.
Adult
25 mg PO tid with first bite of food at each meal; increase dose to 50 mg tid after 4-8 wk; not to exceed 100 mg tid
Pediatric
Not established
May decrease absorption and bioavailability of digoxin, propranolol, and ranitidine; digestive enzymes such as amylase and pancreatin may reduce effects of miglitol; may increase hypoglycemic potential of sulfonylureas
Documented hypersensitivity; diabetic ketoacidosis; colonic ulceration; partial intestinal obstruction or predisposition to intestinal obstruction; inflammatory bowel disease
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
May cause GI symptoms; not recommended for patients with significant renal dysfunction
Thiazolinediones (glitazones)
The first of this class, troglitazone was removed from the US market due to fatal hepatic necrosis.
Rosiglitazone is an antidiabetic agent (thiazolidinedione derivative) that improves glycemic control by improving insulin sensitivity. The drug is highly selective and is a potent agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and use, thereby reducing blood glucose concentrations and reducing hyperinsulinemia. Potent PPAR-gamma agonists have been shown to increase the incidence of edema.
The controversial results of a recently published meta-analysis reporting the increased risk of myocardial infarction and heart-related death in patients treated with rosiglitazone prompted the US Food and Drug Administration (FDA) to issue an alert on May 21, 2007, to patients and healthcare professionals, enjoining patients to discuss the issue with their physician in order to take individualized decisions regarding their care. A large scale phase IV trial specifically designed to study cardiovascular outcomes of rosiglitazone is underway. Whether this warning also applies to the other thiazolidinedione, pioglitazone, is unknown.
In the RECORD trial, cardiovascular outcomes were assessed after adding rosiglitazone to metformin or sulfonylurea regimens for type 2 diabetes mellitus.4 The study was a multicenter, open-label trial that included 4447 patients with mean HbA1c of 7.9%. Follow-up of the 2 combinations took place over 5-7 years. No difference was observed between the 2 groups for cardiovascular death, myocardial infarction, and stroke; 61 patients who received rosiglitazone experienced heart failure that caused either hospital admission or death compared with 29 patients in the active control group (hazard ratio [HR] 2.10, 1.35-3.27 risk difference per 1000 person-years 2.6, 2.2-4.1).
Noncardiovascular adverse effects included increased upper and distal lower limb fracture rates, particularly in women. At 5 years, mean HbA1c was lower in the rosiglitazone group compared with the active control group. Results of this study found that use of rosiglitazone for type 2 diabetes mellitus increases risk of heart failure. Additionally, the risk for select fractures is increased, particularly in women.
For more information, see The FDA’s Safety Alert on Avandia. The online meta-analysis is titled " Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. " Additionally, responses to the controversy can be viewed at the Heartwire news (theheart.org from WebMD) including the following articles:
- " Rosiglitazone increases MI and CV death in meta-analysis. "
- " The rosiglitazone aftermath: Legitimate concerns or hype? "
- " RECORD interim analysis of rosiglitazone safety: No clear-cut answers. "
- " Rosiglitazone evaluated for cardiovascular outcomes-An interim analysis. "
- " Coronary heart disease outcomes in patients receiving antidiabetic agents. "
Rosiglitazone (Avandia)
Insulin sensitizer with major effect in stimulation of glucose uptake in skeletal muscle and adipose tissue. Lowers plasma insulin levels. Used to treat type 2 diabetes associated with insulin resistance.
Adult
4-8 mg/d qd or divided bid
Pediatric
Not established
In combination with insulin or oral hypoglycemics (eg, sulfonylureas) may increase risk for hypoglycemia
Documented hypersensitivity; active liver disease; ketoacidosis; type 1 diabetes
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Monitor transaminases; discontinue if alanine aminotransferase (ALT) level rises above 3X upper limit of reference range; caution in edema and congestive heart failure; may decrease hemoglobin, hematocrit, and WBC counts
Pioglitazone (Actos)
Improves target-cell response to insulin without increasing insulin secretion from pancreas. Decreases hepatic glucose output and increases insulin-dependent glucose use in skeletal muscle and, possibly, liver and adipose tissue.
Adult
15-30 mg PO qd; may increase; not to exceed 45 mg/d
Pediatric
Not established
May reduce plasma concentrations of contraceptives containing ethinyl estradiol and norethindrone; laboratory data suggest ketoconazole may inhibit metabolism (closely monitor blood glucose levels); combination with insulin or oral hypoglycemics (eg, sulfonylureas), may increase risk for hypoglycemia
Documented hypersensitivity; active liver disease; ketoacidosis; type 1 diabetes
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Monitor transaminases; discontinue if ALT rises above 3X upper limit of reference range; caution in edema and congestive heart failure; may decrease hemoglobin, hematocrit, and WBC counts
Incretin Mimetic
Exenatide enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying.
Exenatide (Byetta)
Incretin mimetic agent that mimics glucose-dependent insulin secretion and several other antihyperglycemic actions of incretins. Improves glycemic control in patients with type 2 diabetes mellitus by enhancing glucose-dependent insulin secretion by pancreatic beta cells, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. Drug's 39–amino acid sequence partially overlaps that of the human incretin, glucagonlike peptide-1. Indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes who are taking metformin or a sulfonylurea but have not achieved glycemic control.
Adult
5 μ g SC bid; administer at any time within the 60-minute period before the morning and evening meals (or before the 2 main meals of the day, approximately 6 h or more apart)
Based on clinical response, the dose of exenatide can be increased to 10 μ g bid after 30 d of therapy
Pediatric
Not established
Data limited; coadministration decreases digoxin Cmax and delays Tmax, decreases lovastatin AUC and Cmax, delays lisinopril Tmax, and decreases acetaminophen AUC and C max, but these pharmacokinetic alterations do not appear to be clinically significant; may decrease absorption of orally administered drugs (take drugs requiring rapid absorption, eg, oral contraceptives, antibiotics, at least 1 h before exenatide)
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established
Precautions
Do not administer after meals; administer in thigh, abdomen, or upper arm; may cause hypoglycemia, nausea, vomiting, diarrhea, jittery feeling, dizziness, headache, or dyspepsia; may develop antibodies to protein contents
Amylin analogue
Synthetic analogue of human amylin, a naturally occurring hormone made in pancreas beta cells. Slows gastric emptying, suppresses postprandial glucagon secretion, and regulates food intake through centrally mediated appetite modulation. Indicated to treat type 1 or type 2 diabetes in combination with insulin. Administered before mealtime for patients who have not achieved desired glucose control despite optimal insulin therapy. Helps achieve lower blood glucose levels after meals, less fluctuation of blood glucose levels during the day, and improvement of long-term control of glucose levels (ie, Hgb A1C levels) compared with insulin alone. Additionally, less insulin use and reduction in body weight also observed.
Pramlintide (Symlin)
Synthetic analogue of human amylin, a naturally occurring hormone made in pancreas beta cells. Slows gastric emptying, suppresses postprandial glucagon secretion, and regulates food intake through centrally mediated appetite modulation. Indicated to treat type 1 or type 2 diabetes in combination with insulin. Administered before mealtime for patients who have not achieved desired glucose control despite optimal insulin therapy. Helps achieve lower blood glucose levels after meals, less fluctuation of blood glucose levels during the day, and improvement of long-term control of glucose levels (ie, Hgb A1C levels) compared with insulin alone. Additionally, less insulin use and reduction in body weight also observed.
Adult
Type 1: 15 μ g SC ac initially; titrate upward in 15-μ g increments (if no significant nausea occurs for 3-7 d) to maintenance dose of 30-60 μ g/dose; insulin dose must initially be decreased during initiation phase; once target pramlintide dose achieved, optimize insulin to maintain glycemic control
Type 2: 60 μ g SC ac initially; titrate upward (if no significant nausea occurs for at least 3 d) to maintenance dose of 120 μ g/dose; insulin dose must initially be decreased during initiation phase; once target pramlintide dose achieved, optimize insulin to maintain glycemic control
Pediatric
Not established
Do not use with other drugs that slow gastric emptying (eg, anticholinergic agents such as atropine) or drugs that slow intestinal nutrient absorption (eg, alpha-glucosidase); may delay absorption of concomitantly administered oral drugs, to avoid this effect; administer other drug 1 h before or 2 h after pramlintide
Documented hypersensitivity to pramlintide, any of its components, or metacresol; gastroparesis; hypoglycemia unawareness
Pregnancy
C - Safety for use during pregnancy has not been established
Precautions
Increases risk of insulin-induced severe hypoglycemia, especially with type 1 diabetes or gastroparesis; reduce insulin dose in all patients (either type 2 or type 1) when initiating therapy (monitor blood glucose and adjust insulin dose during initiation phase); common adverse effects include GI complaints, especially nausea (incidence decreased when dose increased gradually); always use separate insulin syringe to measure and administer, do not mix in same syringe as insulin (insulin alters pharmacokinetics); may cause local redness, swelling, or itching at injection site; do not administer unless ingesting major meal (ie, >250 calories or 30 g of carbohydrates)
Dipeptidyl peptidase IV (DPP-4) inhibitor
This agent blocks the action of dipeptidyl peptidase IV (DDP-4), which is known to degrade incretin.
Sitagliptin (Januvia)
First of new class of antidiabetic agents known as DPP-4 inhibitors. Blocks the enzyme DPP-4, which is known to degrade incretin hormones. Increases concentrations of active intact incretin hormones (GLP-1, GIP). The hormones stimulate insulin release in response to increased blood glucose levels following meals. This action enhances glycemic control. Indicated for diabetes type 2 as monotherapy or combined with metformin or a peroxisome proliferator–activated receptor gamma (PPAR-gamma) agonist (eg, thiazolidinediones).
Adult
100 mg PO qd with or without food
CrCl >30 to <50 mL/min: 50 mg PO qd
CrCl <30 mL/min: 25 mg PO qd
Pediatric
Not established
Data limited; caution with other drugs that decrease glucose
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks
Precautions
Common adverse effects include upper respiratory tract infection, nasopharyngitis, and headache; assess renal function before initiating therapy and periodically thereafter; decrease dose with moderate or severe renal insufficiency
More on Diabetes Mellitus, Type 2 |
| Overview: Diabetes Mellitus, Type 2 |
| Differential Diagnoses & Workup: Diabetes Mellitus, Type 2 |
 Treatment & Medication: Diabetes Mellitus, Type 2 |
| Follow-up: Diabetes Mellitus, Type 2 |
| References |
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References
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Further Reading
Keywords
diabetes mellitus type 2, type 2 diabetes mellitus, NIDDM, non–insulin-dependent diabetes mellitus, adult-onset diabetes mellitus, type 2 diabetes mellitus, insulin resistance, type 2 diabetes, diabetes, type 2 diabetes in children
