[Developed - April 1994; September 1995revised; June 1996; June 1997; June 1998; July 1999; June 2000; June 2001; September 2001; July 2002; June 2003; October 2007revised; November 2007, February 2008; January 2011]
Information on indications for use or diagnosis is assumed to be unavailable. All criteria may be applied retrospectively; prospective application is indicated with [*].
1.* Dosage
Oral antidiabetic agents are FDA-approved for use in type 2 diabetics as monotherapy or in combination with other oral antidiabetic agents or insulin, when the single agent alone, in addition to diet and exercise, does not provide sufficient glycemic control.
Oral sulfonylureas reduce blood glucose by stimulating insulin from pancreatic beta-cells as well as increasing responsiveness in insulin-sensitive tissues. Although structurally dissimilar from oral sulfonylureas, meglitinides also stimulate insulin secretion by inhibiting ATP-sensitive potassium channels in pancreatic beta-cells.
Metformin is an oral hypoglycemic agent that improves glycemic control by decreasing hepatic glucose production and intestinal glucose absorption as well as improving insulin sensitivity through increased peripheral glucose uptake and utilization. Alpha glucosidase inhibitors inhibit the ability of alpha glucosidase to convert nonabsorbable dietary starch and sucrose into absorbable glucose, which results in slower glucose absorption and reduced postprandial glucose levels.
The bile acid sequestrant, colesevelam, is FDA-approved for use to manage primary hyperlipidemia as well as type 2 diabetes as an adjunct to diet and exercise. The mechanism by which colesevelam lowers hemoglobin A1c (HbA1c) and improves glycemic control is unknown. Bromocriptine, a dopamine agonist, is FDA-approved as Cycloset® to manage glycemic control in type 2 diabetes as an adjunct to diet and exercise through a currently undetermined mechanism.
The incretin hormones, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been identified as important factors in glucose homeostasis. Released from the gut postprandially, GLP-1 and GIP stimulate insulin secretion from pancreatic beta cells in response to normal or elevated blood glucose concentrations. GLP-1 also lowers glucagon excretion from pancreatic beta cells, which results in reduced hepatic glucose production, and also reduces appetite, slows gastric emptying, and improves β-cell function. When administered intravenously or subcutaneously, GLP-1 is effective in treating type 2 diabetes. Unfortunately, both GLP-1 and GIP are rapidly degraded by dipeptidyl peptidase IV (DPP-IV); therefore, research has been focused on preventing degradation by inhibiting the DPP-IV enzyme. The newly developed DPP-IV inhibitors reduce inactivation of incretin hormones and improve glycemic control in type 2 diabetic patients without significant weight gain.
Thiazolidinediones are potent agonists of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), receptors important for insulin action which are located in adipose tissue, liver and skeletal muscle. Activation of these receptors affects the transcription of genes responsible for control of glucose and lipid metabolism. These agents, in the presence of insulin, decrease insulin resistance in the liver and at peripheral sites and improve insulin-dependent glucose disposal and reduce hepatic glucose output. The thiazolidinediones, rosiglitazone and pioglitazone, have been associated with an increased risk of congestive heart failure most likely due to a greater incidence of fluid retention/edema associated with this drug class. Patients should be closely monitored for signs and symptoms of CHF, and thiazolidinedione dosages reduced or discontinued should symptoms develop. Thiazolidinediones are contraindicated for use in NYHA Class III or IV heart failure and are not recommended in patients with symptomatic heart failure.
Recent data have documented an increased risk of heart attack and heart-related deaths in patients prescribed rosiglitazone. The FDA have determined that while the evidence documenting increased cardiovascular ischemic risks with rosiglitazone are not robust or consistent, there are enough areas of concern to warrant significant restrictions on rosiglitazone use. Rosiglitazone is now only approved for use in patients with type 2 diabetes who cannot maintain glycemic control with any other antidiabetic medication.
Female patients treated with thiazolidinediones may be at increased risk for developing fractures. These agents have been shown to stimulate formation of more adipocytes rather than osteoblasts in bone. Thiazolidinediones may also decrease hip and femoral neck bone mineral density in older diabetic patients. Fractures currently reported with thiazolidinedione use have been limited to the humerus, hand and foot in female patients only. Further assessment of thiazolidinedione adverse skeletal effects is necessary to determine the risk-benefit ratio of these agents in diabetic patients. Female patients at higher fracture risk should be considered for bone mineral density assessment and bone strengthening therapies (e.g., calcium, vitamin D, bisphosphonates) prior to therapy initiation with thiazolidinediones.
Adults
Maximum recommended daily doses for available oral antidiabetic agents, both as monotherapy and as combination therapy, are summarized in Tables 1 and 2. Prescribed dosages exceeding these recommendations will be reviewed.
| DRUG | AVAILABLE DOSAGE STRENGTHS | MAXIMUM DAILY DOSE |
|---|---|---|
| ALPHA-GLUCOSIDASE INHIBITORS (AGIs) —Acarbose (Precose®): | 25 mg, 50 mg, 100 mg tablets | patients < 60 kg: 150 mg/day, in divided doses patients > 60 kg: 300 mg/day, in divided doses |
| ALPHA-GLUCOSIDASE INHIBITORS (AGIs) —Miglitol (Glyset®) | 25 mg, 50 mg, 100 mg tablets | 300 mg/day, in divided doses |
| BIGUANIDES — Metformin immediate-release (Glucophage®) |
500 mg, 850 mg, 1000 mg tablets |
2550 mg/day |
| BIGUANIDES — Metformin extended-release (Glucophage XR®, Fortamet®, Glumetza®, various generics) |
500 mg, 750 mg, 1000 mg tablets | 2000 mg/day (2500 mg Fortamet®) |
| BIGUANIDES — oral solution (Riomet®) | 500 mg/5ml | 2550 mg/day |
| BILE ACID SEQUESTRANTS — Colesevelam (Welchol®) | 625 mg tablets, 1.875 g powder packet, 3.75 g powder packet | 3.75 g/day, in single or divided doses |
| DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS — Saxagliptin (Onglyza®) | 2.5 mg, 5 mg tablets | 5 mg/day |
| DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS — Sitagliptin (Januvia®) | 25 mg, 50 mg, 100 mg tablets | 100 mg/day |
| DOPAMINE AGONISTS — Bromocriptine (Cycloset®) | 0.8 mg tablets | 4.8 mg/day |
| MEGLITINIDES — Nateglinide (Starlix®) | 60 mg, 120 mg tablets | 360 mg/day |
| MEGLITINIDES — Repaglinide (Prandin®) | 0.5 mg, 1 mg, 2 mg tablets | 16 mg/day |
| SULFONYLUREAS — Chlorpropamide (various generics) | 100 mg, 250 mg tablets | 750 mg/day |
| SULFONYLUREAS — Glimepiride (Amaryl®, various generics) | 1 mg, 2 mg, 4 mg tablets | 8 mg/day |
| SULFONYLUREAS — Glipizide immediate-release: (Glucotrol®, various generics) |
5 mg, 10 mg tablets | 40 mg/day |
| SULFONYLUREAS — Glipizide extended-release: (Glucotrol XL®) |
2.5 mg, 5 mg, 10 mg tablets | 20 mg/day |
| SULFONYLUREAS — Glyburide nonmicronized (DiaBeta®, various generics) |
1.25 mg, 2.5 mg, 5 mg tablets |
20 mg/day |
| SULFONYLUREAS — Glyburide micronized (Glynase®, various generics) |
1.5 mg, 3 mg, 6 mg tablets | 12 mg/day |
| SULFONYLUREAS — Tolazamide (various generics) | 100 mg, 250 mg, 500 mg tablets | 1000 mg/day |
| SULFONYLUREAS — Tolbutamide (Orinase®, various generics) | 500 mg tablet | 3000 mg/day |
| THIAZOLIDINEDIONES (TZDs) — Pioglitazone (Actos®) | 15 mg, 30 mg, 45 mg tablets | 45 mg/day |
| THIAZOLIDINEDIONES (TZDs) — Rosiglitazone (Avandia®) | 2 mg, 4 mg, 8 mg tablets | 8 mg/day |
| DRUG | AVAILABLE DOSAGE STRENGTH | MAXIMUM DAILY DOSE |
|---|---|---|
| Glipizide/Metformin (Metaglip®, generic) | 2.5 mg/250 mg, 2.5 mg/500 mg, 5 mg/500 mg tablets | 20 mg/2000 mg per day |
| Glyburide/ Metformin (Glucovance®, generic) | 1.25 mg/250 mg, 2.5 mg/500 mg, 5 mg/500 mg tablets | 20 mg/2000 mg per day |
| Pioglitazone/Glimepiride (Duetact®) | 30 mg/2 mg, 30 mg/4 mg tablets | 45 mg/8 mg per day |
| Repaglinide/Metformin (PrandiMet®) | 1 mg /500 mg, 2 mg/500 mg tablets | 10 mg/2500 mg per day (4 mg/1000 mg per meal) |
| Pioglitazone/Metformin immediate-release (ActoPlus Met®) extended-release (ActoPlus Met XR®) |
15 mg/500 mg, 15 mg/850 mg tablets 15 mg/1000 mg, 30 mg/1000 mg tablets |
45 mg/2550 mg per day 45 mg/2000 mg per day |
| Rosiglitazone/Glimepiride (Avandaryl®) | 4 mg/1 mg, 4 mg/2 mg, 4 mg/4 mg, 8 mg/2 mg, 8 mg/4 mg tablets |
8 mg/4 mg per day |
| Rosiglitazone/Metformin (Avandamet®) | 2 mg/500 mg, 2 mg/1000 mg, 4 mg/500 mg, 4 mg/1000 mg tablets | 8 mg/2000 mg per day |
| Saxagliptin/Metformin (Kombiglyze XR®) | 5 mg/500 mg, 2.5 mg/1000 mg, 5 mg/1000 mg tablets | 5 mg/2000 mg per day |
| Sitagliptin/Metformin (Janumet®) | 50 mg/500 mg, 50 mg/1000 mg tablets | 100 mg/2000 mg per day |
Sitagliptin dosages should be adjusted in adult patients with renal insufficiency. Patients with moderate renal insufficiency (CrCl > 30 to < 50 ml/min corresponding to serum creatinine levels between 1.7 and 3 mg/dl in men and 1.5 and 2.5 mg/dl in women) should receive sitagliptin 50 mg daily, while patients with severe renal insufficiency (CrCl < 30 ml/min corresponding to serum creatinine levels in men > 3 mg/dl or > 2.5 mg/dl in women) or those patients with end stage renal disease requiring hemodialysis or peritoneal dialysis should receive sitagliptin 25 mg daily. Saxagliptin dosages should be reduced to 2.5 mg once daily in patients with CrCl < 50 ml/min or in patients prescribed a strong CYP3A4 inhibitor (e.g., ketoconazole).
Pediatrics
Oral sulfonylureas, alpha-glucosidase inhibitors, pioglitazone, meglitinides and DPP-4 inhibitors are not FDA-approved for use in pediatric patients as safety and efficacy have not been determined in this patient population. Sufficient data are not available to assess rosiglitazone safety and efficacy in pediatric patients.Metformin immediate-release is FDA-approved for use in pediatric type 2 diabetic patients 10 years of age and older as an adjunct to diet in exercise to aid in controlling blood glucose. Maximum recommended oral antidiabetic doses in pediatric patients are summarized in Table 3. Dosages exceeding these recommendations will be reviewed.
| DRUG | MAXIMUM RECOMMENDED DOSE |
|---|---|
| Monotherapy: Metformin immediate-release |
> 10 years of age: 2000 mg/day, in divided doses |
2. Duration of Therapy
There is no basis for limiting the duration of oral antidiabetic therapy as diabetes is a chronic disorder.
3.* Duplicative Therapy
Administering two or more oral sulfonylureas concurrently is not justified. The concomitant use of two or more oral sulfonylureas will be reviewed.
The combined use of nateglinide or repaglinide and oral sulfonylureas is not justified as both drug classes stimulate insulin secretion. Concurrent administration of nateglinide or repaglinide and oral sulfonylureas will be reviewed.
The risk of hypoglycemia may increase when acarbose or miglitol is added to pre-existing oral hypoglycemic or insulin therapy. Blood glucose levels should be monitored closely when alpha glucosidase inhibitor therapy is initiated in patients already receiving oral hypoglycemic or insulin therapy.
Adjunctive administration of rosiglitazone and insulin is not recommended as a greater incidence of myocardial ischemic events was observed in clinical trials when rosiglitazone was added to insulin therapy.
Concurrent administration of thiazolidinediones or metformin with sulfonylureas may result in an increased frequency of hypoglycemic episodes. Blood glucose levels should be closely monitored if patients are prescribed thiazolidinediones or metformin and oral sulfonylureas concomitantly, and oral sulfonylurea dosage reductions should be considered.
Concurrent administration of sitagliptin and glimepiride, with or without metformin, has resulted in significant reductions in HbA1c and fasting plasma glucose compared to placebo. The risk of hypoglycemia with sitagliptin in combination with metformin and pioglitazone is comparable to that observed with placebo; however, the incidence of hypoglycemia in patients prescribed sitagliptin concurrently with glimepiride is greater than that seen with placebo. The incidence of hypoglycemia in patients prescribed sitagliptin and insulin concurrently has not been adequately evaluated. Therefore, blood glucose levels should be closely monitored if patients are prescribed sitagliptin and oral sulfonylureas or insulin concomitantly, and oral sulfonylurea dosage reductions should be considered.
Saxagliptin, when utilized as monotherapy or combined with metformin, sulfonylureas, or thiazolidinediones, has significantly reduced HbA1c levels and improved glycemic control compared to placebo. Hypoglycemia was comparable with saxagliptin and placebo when used as monotherapy and did not increase when saxagliptin was combined with metformin or a TZD. However, a larger percentage of patients experienced hypoglycemia when saxagliptin was combined with glyburide compared to placebo. Like sitagliptin, the incidence of hypoglycemia when saxagliptin is combined with insulin therapy has not been adequately evaluated. Consequently, blood glucose levels should be closely monitored when saxagliptin is utilized in combination with oral sulfonylureas or insulin, with saxagliptin dosage adjustments made as necessary.
4.* Drug-Drug Interactions
Patient profiles will be reviewed to identify those drug regimens which may result in clinically significant drug-drug interactions.
Drug-drug interactions considered clinically relevant for oral antidiabetic agents are summarized in Table 4. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed:
| TARGET DRUG | INTERACTING DRUG | INTERACTION | RECOMMENDATIONS | CLINICAL SIGNIFICANCE |
|---|---|---|---|---|
| acarbose | digoxin | adjunctive administration may result in decreased digoxin levels; acarbose most likely impairs digoxin absorption | avoid concurrent administration; separate administration by 6 hours to avoid interaction; monitor digoxin levels | 2-major (CP*) 2 (DIF) |
| AGIs | digestive enzymes | combined therapy may result in decreased AGI absorption, reduced pharmacologic effects | avoid concurrent administration | moderate (DrugReax) 2-major (CP) |
| antidiabetic agents (ADAs) | ACE inhibitors/ angiotensin receptor blockers (ARBs) | combined therapy may result in increased risk of hypoglycemia, most likely due to ACE inhibitor/ARB improved insulin sensitivity | monitor glycemic control when initiating or changing therapy | 3-moderate (CP) 2 (DIF) |
| ADAs | atypical antipsychotics (AAs) | combined therapy may result in loss of glycemic control; AAs may increase insulin resistance or inhibit beta cells | monitor for loss of glycemic control; adjust doses as necessary | 3-moderate (CP) |
| ADAs | beta blockers (BB) | BB may prolong hypoglycemia (interference with mobilization of glycogen stores), promote hyperglycemia (inhibit insulin secretion/decrease tissue insulin sensitivity), as well as mask signs/symptoms of hypoglycemia | administer cautiously together; consider cardioselective BB due to lesser effects on glucose metabolism, less masking of hypoglycemic signs/symptoms | moderate (DrugReax) 3-moderate (CP) |
| ADAs | fluoroquinolones | combined administration may increase risk of hyper- or hypoglycemia; mechanism unknown | closely monitor serum glucose levels; adjust ADA doses as needed | major (DrugReax) 3-moderate (CP) |
| ADAs | MAOIs | adjunctive therapy may result in additive glucose-lowering effects; MAOIs may stimulate insulin secretion | closely monitor serum glucose levels; decrease antidiabetic agent doses as necessary | moderate (DrugReax) 3-moderate (CP) 2 (DIF) |
| ADAs | thiazide diuretics | combined therapy may antagonize hypoglycemic effects of ADAs as thiazides increase blood glucose levels in dose-related manner | utilize lower thiazide doses, if possible; monitor serum glucose levels; adjust ADA doses as needed | 3-moderate (CP) 2 (DIF) |
| bromocriptine | ergot alkaloids | combined therapy may increase risk of ergot toxicity (e.g., angina, paresthesias) as bromocriptine is ergot derivative | avoid using together | 1-severe (CP) |
| bromocriptine | metoclopramide | combined therapy may attenuate bromocriptine pharmacological effects; metoclopramide is dopamine antagonist | avoid concurrent use | 2-major (CP) |
| bromocriptine | select macrolides (e.g., clarithromycin, erythromycin) | potential for increased bromocriptine pharmacologic/adverse effects due to decreased hepatic metabolism by macrolide | monitor patient for adverse effects; decrease bromocriptine dose as necessary | moderate (DrugReax) 3-moderate (CP) 2 (DIF) |
| bromocriptine | serotonin-receptor agonists (e.g., sumatriptan) | increased risk of serious coronary ischemia due to potential for additive vasospasm | avoid concurrent administration within 24 hours of each other | 2-major (CP) |
| bromocriptine | drugs metabolized by CYP3A4 (e.g., tacrolimus, cyclosporine, sirolimus) | potential for decreased cyclosporine/ sirolimus/tacrolimus clearance, enhanced pharmacologic/adverse effects; bromocriptine is CYP3A4 inhibitor | monitor for increased pharmacologic/adverse effects; consider reducing dose of CYP3A4 substrate | 2-major (CP) |
| colesevelam | cyclosporine | decreased cyclosporine peak serum concentrations and AUC with combined therapy | administer cyclosporine at least 4 hours prior to colesevelam; monitor serum cyclosporine levels | 3-moderate (CP) |
| colesevelam | oral contraceptives (OC) | decreased peak ethinyl estradiol/ norethindrone serum levels, AUC with combined therapy | administer OC at least 4 hours before colesevelam | 3-moderate (CP) |
| colesevelam | thyroid hormones (TH) (e.g., levothyroxine, liothyronine) | combined therapy may cause reduced thyroid hormone absorption due to nonspecific binding to colesevelam | take TH at least 4 hours prior to colesevelam; monitor for adequate thyroid response; adjust TH dose as needed | moderate (DrugReax) 3-moderate (CP) 2 (DIF) |
| glimepiride | voriconazole | combined therapy may increase glimepiride levels and risk of hypoglycemia; voriconazole inhibits CYP2C9, glimepiride metabolized by CYP2C9 | monitor for hypoglycemia; consider lowering glimepiride dose | major (DrugReax) 3-moderate (CP) |
| glyburide, TZDs | bosentan | increased risk of elevated liver enzymes when used concurrently; bosentan, a CYP2C9 and CYP3A4 inducer, may decrease glyburide and TZD levels/reduce hypoglycemic effects; glyburide, rosiglitazone metabolized by CYP2C9, pioglitazone metabolized by CYP3A4 | combined therapy contraindicated; choose alternative ADA | glyburide -1-severe; TZDs - 2-major (CP) glyburide -contraindicated (DrugReax) glyburide -1 (DIF) |
| meglitinides, sulfonylureas, TZDs | rifamycins | combined therapy may result in reduced ADA serum levels and loss of hypoglycemic control due to enhanced ADA hepatic metabolism by rifamycin | closely monitor serum glucose levels; adjust ADA dose as necessary | moderate (DrugReax) 4-minor (CP) 2 (DIF) |
| metformin | dofetilide | increased risk of lactic acidosis; dofetilide decreases metformin elimination by competing for renal tubular transport system; potential for increased dofetilide serum concentrations and cardiotoxicity risk | manufacturer recommends avoiding concurrent use | 1-severe (CP) major (DrugReax) |
| pioglitazone | estrogens, progestins, OCs | combined therapy may attenuate pioglitazone hypoglycemic effects; estrogens, progestins, OCs impair glucose tolerance; also, pioglitazone lowers estrogen levels when used as combined therapy with OCs, potentially resulting in reduced OC effectiveness | monitor for changes in glycemic control; may consider higher dose OC or alternative form of contraception | 2-major (CP) |
| pioglitazone | tolvaptan | combined therapy may decreases tolvaptan concentrations; pioglitazone is CYP3A4 inducer, tolvaptan is metabolized by CYP3A4 | avoid concurrent use if possible; if combined therapy necessary, increase tolvaptan dose and monitor efficacy | major (DrugReax) |
| repaglinide, TZDs | gemfibrozil | combined therapy increases potential for elevated repaglinide or TZD levels/amplified repaglinide or TZD hypoglycemic effects due to gemfibrozil inhibition of CYP2C8; repaglinide, TZDs metabolized by CYP2C8 | avoid concurrent administration; if combination cannot be avoided, use lower repaglinide dose | contraindicated (DrugReax) 1-severe (CP) 2 (DIF) |
| repaglinide | CYP3A4 inhibitors (e.g., rifamycins, macrolides, itraconazole) | combined therapy may significantly increase repaglinide concentrations and increase hypoglycemia risk; repaglinide metabolized by CYP3A4 | administer cautiously together; monitor for hypoglycemia; adjust repaglinide dose as necessary | itraconazole-major ; others – moderate (DrugReax) 2-major (CP) 2 (DIF) |
| repaglinide | cyclosporine | cyclosporine is CYP3A4 inhibitor, also inhibits uptake of repaglinide into liver by inhibiting OATP1B1, which increases risk of elevated repaglinide levels and hypoglycemia when given concurrently | administer cautiously together; closely monitor glycemic control; adjust repaglinide dose as necessary | 2-major (CP) 2 (DIF) |
| repaglinide | isophane insulin (NPH) | combined therapy caused myocardial ischemia in clinical trials | avoid concurrent administration | 2-major (CP) |
| rosiglitazone | nitrates | in clinical trials, increased risk of myocardial ischemia in patients receiving combined therapy | avoid concurrent administration (manufacturer recommendations) | 2-major (CP) |
| saxagliptin | CYP3A4/5 inhibitors (e.g., ketoconazole, erythromycin, fluconazole) | combined therapy may increase saxagliptin levels and risk of hypoglycemia; saxagliptin metabolized by CYP3A4/5 | utilize lower saxagliptin dose (2.5 mg daily) with strong CYP3A4/5 inhibitors (e.g., ketoconazole); adjunctive therapy with moderate CYP3A4/5 inhibitors does not warrant dosage adjustments | 2-major (CP) |
| sulfonylureas | methotrexate | concurrent administration may result in methotrexate displacement from protein binding sites and increased risk of methotrexate toxicity | consider avoiding combination; watch for signs of toxicity | 2-major (CP) |
| sulfonylureas | sulfonamides | combined therapy may exaggerate sulfonylurea hypoglycemic effects; sulfonamides may inhibit sulfonylurea metabolism or displace sulfonylurea from protein binding site; glipizide, glyburide not significantly affected due to nonionic binding of these agents | use combination cautiously; closely monitor serum glucose levels, observe for signs/symptoms of hypoglycemia, reduce sulfonylurea dose as necessary | moderate (DrugReax) 3-moderate (CP) 2 (DIF) |
| tolbutamide | CYP2C9 inhibitors (e.g., imatinib, sorafenib, delavirdine) | combined therapy may increase tolbutamide serum concentrations, increase risk of hypoglycemia | closely monitor serum glucose levels | 2-major (CP) |
| thiazolidinediones | insulins | combined therapy associated with increased risk of heart failure and/or edema and myocardial ischemic events | manufacturer recommends avoiding concurrent use | 2-major (CP) |
References
- DRUGDEX® System (electronic version). Thomson Reuters (Healthcare) Inc., Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com.libproxy.uthscsa.edu. Accessed January 18th, 2011.
- Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2011. Available at: http://www.clinicalpharmacology.com. Accessed January 18th, 2011.
- Drug Facts and Comparisons. Clin-eguide [database online]. St. Louis, MO: Wolters Kluwer Health, Inc; 2011. Available at: http://clineguide.com. Accessed January 18th, 2011.
- Metformin extended-release tablets (Fortamet®) Package Insert. Shionogi Pharma, Inc., February 2010.
- Metformin extended-release tablets (Glumetza®) Package Insert. Depomed, Inc., December 2008.
- FDA significantly restricts access to the diabetes drug Avandia. (9/23/10) Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm226956.htm. Accessed January 18th, 2011.
- Food and Drug Administration. Center for Drug Evaluation and Research. Decision on continued marketing of rosiglitazone (Avandia, Avandamet, Avandaryl). (Reference ID # 2839558) Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM226959.pdf. Accessed January 18th, 2011.
- Colesevelam tablets, oral suspension (Welchol®) Package Insert. Daiichi Sankyo, Inc., February 2010.
- Bromocriptine tablets (Cycloset®) Package Insert. Santarus, Inc., September 2010.
- AHFS Drug Information 2011. Jackson, WY: Teton Data Systems, Version 7.0.14, 2010. Stat!Ref Electronic Medical Library. Available at: http://online.statref.com.libproxy.uthscsa.edu/. Accessed January 18th, 2011.
- Drug interaction facts. Clin-eguide [database online]. St. Louis, MO: Wolters Kluwer Health, Inc; 2011. Available at: http://clineguide.com. Accessed January 18th, 2011.
- DRUG-REAX® System (electronic version). Thomson Reuters (Healthcare) Inc., Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com.libproxy.uthscsa.edu. Accessed January 18th, 2011.
- Metaglip and Avandamet for type 2 diabetes. Med Lett Drugs Ther. 2002;44:107-9.
- Scheen AJ. Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Saf. 2005;28:601-31.
- Halas CJ. Nateglinide. Am J Health Syst Pharm. 2001;58:1200-5.
- Plosker GL, Figgitt DP. Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus. Pharmacoeconomics. 2004;22:389-411.
- Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147:386-99.
- van de Laar FA, Lucassen PL, Akkermans RP, et al. Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose. Cochrane Database Syst Rev. 2006;4:CD005061.
- Black C, Donnelly P, McIntyre L, et al. Meglitinide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;2:CD004654.
- Singh S, Loke YK. Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA. 2007;298:1189-95.
- Lincoff AM. Wolski K. Nicholls SJ. Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298:1180-8.
- Home PD, Jones NP, Pocock SJ, et al., for the RECORD Study Group. Rosiglitazone RECORD study: glucose control outcomes at 18 months. Diabet Med. 2007;24:626-34.
- Bloomgarden ZT. Thiazolidinediones. Diabetes Care. 2005;28:488-93.
- Granberry MC, Hawkins JB, Franks AM. Thiazolidinediones in patients with type 2 diabetes mellitus and heart failure. Am J Health Syst Pharm. 2007;64:931-6.
- Kahn SE, Haffner SM, Heise MA, et al, and the ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427-43.
- Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (Prospective Pioglitazone Clinical Trial in Macrovascular Events): a randomized controlled trial. Lancet. 2005; 366:1279-89.
- Dargie HJ, Hildebrandt PR, Riegger GA, et al. A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association Functional Class I or II Heart Failure. J Am Coll Cardiol. 2007;49:1696-704.
- U.S. Food and Drug Administration. Center for Drug Evaluation and Research. Information for healthcare professionals. Rosiglitazone (marketed as Avandia, Avandamet and Avandaryl). (August 29th, 2007) Available at: http://www.fda.gov/cder/drug/InfoSheets/HCP/rosiglitazone200707HCP.htm. Accessed October 10th, 2007.
- Mascitelli L, Pezzetta F. Thiazolidinediones and the risk of nontraumatic fractures in patients with diabetes. Arch Intern Med. 2006;166:126.
- Short R. Fracture risk a class effect of thiazolidinediones in women. BMJ. 2007;334:551.
- Schwartz AV, Sellmeyer DE. Thiazolidinedione therapy gets complicated: is bone loss the price of improved insulin resistance? Diabetes Care. 2007;30:1670-1.
- Hermansen K, Kipnes M, Luo E, et al, for the Sitagliptin 035 Study Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007;9:733-45.
- Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP, for the Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007;9:194-205.
- Miller SA, St. Onge EL. Sitagliptin: A dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Ann Pharmacother. 2006;40:1336-43.
- Sitagliptin (Januvia) for type 2 diabetes. Med Lett Drugs Ther. 2007;49:1-3.
- Charbonnel B, Karasik A, Liu J, Wu M, Meininger G; Sitagliptin Study 020 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006;29:2638-43.
- Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006;29:2632-7.
- Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P; Sitagliptin Study 019 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006;28:1556-68.
- Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab. 2008;10:376-386.
- Chacra AR, Tan GH, Apanovitch A, et al. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomized controlled trial. Int J Clin Pract. 2009;63(9):1395-1406.
- DeFronzo RA, Hissa MN, Garber AJ, et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes on metformin alone. Diabetes Care. 2009;32(9):1649-55.
- Gaziano JM, Cincotta AH, O'Connor CM, et al. Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. Diabetes Care. 2010;33(7):1503-8.
- Pijl H, Ohashi S, Matsuda M, et al. Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care. 2000;23(8):1154-61.
- Bays HE, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Arch Intern Med. 2008;168(18):1975-83.
- Brunetti L, Hermes-Desantis ER. The role of colesevelam hydrochloride in hypercholesterolemia and type 2 diabetes mellitus. Ann Pharmacother. 2010;44(7):1196-1206.
Prepared by: Drug Information Service, The University of Texas Health Science Center at San Antonio, and the College of Pharmacy, The University of Texas at Austin.