Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update [Entered Retrospectively]

Project Summary Title and Description

Title
Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update [Entered Retrospectively]
Description
Objectives: Given the number of medications available for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices. The objective of this review was to summarize the benefits and harms of medications (metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 [DPP- 4] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists), as monotherapy and in combination, for the treatment of adults with type 2 diabetes; Data Sources: We searched the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from inception through April 2010 for original English-language articles and sought unpublished data from the Food and Drug Administration and others; Review Methods: Two reviewers independently screened titles to identify studies that assessed intermediate outcomes (e.g., hemoglobin A1c [HbA1c]), long-term clinical outcomes (e.g., mortality), and harms (e.g., hypoglycemia) in head-to-head monotherapy or combination therapy comparisons. Two reviewers serially extracted data for each article using standardized protocols, assessed applicability, and independently evaluated study quality; Results: The review included 140 randomized controlled trials and 26 observational studies. We graded evidence as low or insufficient for long-term clinical outcomes of all-cause mortality, cardiovascular disease, nephropathy, and neuropathy. Most medications lowered HbA1c on average by 1 absolute percentage point, but metformin was more efficacious than the DPP-4 inhibitors. Two-drug combinations had similar HbA1c reduction. Compared with metformin, thiazolidinediones and sulfonylureas had a more unfavorable effect on weight (mean difference of +2.6 kg). Metformin decreased low density lipoprotein cholesterol relative to pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a fourfold higher risk of mild/moderate hypoglycemia compared with metformin alone, and, in combination with metformin, had more than a fivefold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas and bone fractures relative to metformin. Diarrhea occurred more often for metformin compared with thiazolidinedione users; Conclusions: Comprehensive information comparing benefits and harms of diabetes medications can facilitate personalized treatment choices for patients. Although the long-term benefits and harms of diabetes medications remain unclear, the evidence supports use of metformin as a first- line agent. Comparisons of two-drug combinations showed little to no difference in HbA1c reduction, but some combinations increased risk for hypoglycemia and other adverse events.
Attribution
N/A
Authors of Report
N/A
Methodology description
We searched the following databases for primary studies for the periods in parentheses: MEDLINE® (1966 to April 2010), Embase® (1974 to April 2010), and the Cochrane Central Register of Controlled Trials (1966 to April 2010). We updated the MEDLINE search to December 2010 for long-term clinical outcomes (i.e., all-cause mortality, cardiovascular morbidity and mortality, nephropathy and neuropathy). We developed a search strategy for MEDLINE, accessed via PubMed, based on an analysis of the medical subject headings (MeSH) terms and text words of key articles identified a priori. Our search strategy was similar to the one used for the initial 2007 review,21 but it included terms for the additional medications included in this review (Appendix B). In addition, we received the following material from the Scientific Resource Center: • Medical reviews of rosiglitazone, pioglitazone, sitagliptin, glyburide, and metformin, combination of metformin and glipizide, combination of metformin and sitagliptin, insulin detemir, exenatide and postmarketing drug safety information on pioglitazone and insulin glargine from the FDA Web site • The Scientific Discussion sections of the European Public Assessment Reports for rosiglitazone, pioglitazone, sitagliptin, combination rosiglitazone and metformin, exenatide, insulin detemir, and insulin glargine • Health Canada Product Monographs for rosiglitazone, pioglitazone, sitagliptin, combination rosiglitazone and metformin, insulin glargine, and insulin detemir • Public registries of clinical trials, such as Clinical Study Results Web site (available at: www.clinicalstudyresults.org) and ClinicalTrials.gov (available at: www.clinicaltrials.gov). We hand searched 15 journals that most likely to publish articles on this topic (see Appendix C) by scanning the table of contents of each issue for relevant citations from February 2009 through September 2009. We also reviewed the reference lists of each included article and relevant review articles. The results of the searches were downloaded and imported into ProCite® version 5 (ISI ResearchSoft, Carlsbad, CA). We scanned for exact article duplicates, author/title duplicates, and title duplicates using the duplication check feature in ProCite.® From ProCite, the articles were uploaded to DistillerSR (Evidence Partners, Ottawa, Ontario, Canada), a Web-based software package developed for systematic review data management. This database was used to track the search results at the levels of title review, abstract review, article inclusion/exclusion, and data abstraction.
PROSPERO
N/A
DOI
10.7301/Z07H1GGV
Notes
*** The systematic review data of this published project was retrospectively imported into SRDR by the Brown EPC on behalf of the Johns Hopkins University Evidence-based Practice Center and the Agency for Healthcare Research and Quality (AHRQ). For access to the full report available on the AHRQ website, follow this link: http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=644 *** This systematic review of the literature will address the following key questions (KQs):  KQ1: In adults age 18 or older with type 2 diabetes mellitus, what is the comparative effectiveness of these treatment options (see list of comparisons) for the intermediate outcomes of glycemic control (in terms of HbA1c), weight, or lipids?  KQ2: In adults age 18 or older with type 2 diabetes mellitus, what is the comparative effectiveness of the treatment options (see list of comparisons) in terms of the following long-term clinical outcomes? • All-cause mortality • Cardiovascular mortality • Cardiovascular and cerebrovascular morbidity (e.g., myocardial infarction and stroke) • Retinopathy • Nephropathy • Neuropathy  KQ3: In adults age 18 or older with type 2 diabetes mellitus, what is the comparative safety of the treatment options (see list of comparisons) in terms of the following adverse events and side effects? • Hypoglycemia • Liver injury • Congestive heart failure • Severe lactic acidosis • Cancer • Severe allergic reactions • Hip and non-hip fractures • Pancreatitis • Cholecystitis • Macular edema or decreased vision • Gastrointestinal side effects. | Abbreviations for Appendix G - Table 2: ACEI = angiotensin-converting enzyme inhibitors; ADA = American Diabetes Association; ALT = alanine aminotransferase; AST = asparate aminotransferase; BMI = body mass index; BP = blood pressure; CAD = coronary artery disease; CHF = congestive heart failure; CK = creatine phosphokinase; CVD = cardiovascular diseases; DBP = diastolic blood pressure; DM = diabetes mellitus; FBG = fasting blood glucose; FPG = fasting plasma glucose; g/day = grams per day; g/dl = grams per deciliter; GFR = glomerular filtration rate; GI disorder = gastrointestinal disorders; HbA1c = hemoglobin A1c; kg = kilogram; kg/m2 = kilograms per meter squaredlbs = pounds; LDL = low density lipoprotein; LVEF = left ventricular ejection fraction; met = metformin; mg = milligram; mg/d = milligrams per day; mg/dL = milligrams per deciliter; mm Hg = millimeters of mercury; mmol/l = millimoles per liter; NCEP ATP III = National Cholesterol Education Program Adult Treatment Panel IIIng/ml = nanograms per milliliter; nmol/l = nanomoles per liter; NR = not reported; NYHA = New York Heart Association; ODM = oral diabetes medications; pmol/l = picomoles per liter; SBP = systolic blood pressure; SGOT = serum glutamyl oxaloacetic transaminase; SGPT = serum glutamyl pyruvic transaminase; SU = sulfonylurea; TZD = thiazolidinedione; U/kg = units per kilogram; UKPDS = The UK Prospective Diabetes Study;US = United States; WHO = World Health Organization; yrs = years | Abbreviations for Appendix G - Table 3: AA = African American; BHI = biphasic human insulin; C = Caucasian; H = Hispanic; kg = kilogram; NPH = neutral protamine Hagedorn; NR = not reported; sd = standard deviation | Abbreviations for Appendix G - Table 6: ALT = alanine aminotransferase; AST = asparate aminotransferase; BID = twice a day; BMI = body mass index; BP = blood pressure; CAD = coronary artery disease; CHF = congestive heart failure; CK = creatine kinase; CVD = cardiovascular diseases; DBP = diastolic blood pressure; DM = diabetes mellitus; FBG = fasting blood glucose; FPG = fasting plasma glucose; g/dl = grams per deciliter; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; ICD-9 = International Statistical Classification of Diseases and Related Health Problems-9; kg = kilogram; kg/m2 = kilogram per meter squared; LDL = low density lipoprotein; LHSVE = Large Health Survey of Veteran Enrollees; LVEF = left ventricular ejection fraction; mg/d = milligrams per day; mg/dl = milligrams/deciliter; mmHg = millimeters of mercury; mmol/L = millimoles per liter; NA = not applicable; nmol/L = nanomoles per liter; NPH = neutral protamine Hagedorn; NR = not reported; NSAID = non-steroidal anti-inflammatory drugs; ODM = oral diabetes medication; PPAR- G = peroxisome proliferator-activated receptor gamma; QD = once a day; RCT = randomized controlled trial; SBP = systolic blood pressure; SGOT = glutamyl oxaloacetic transaminase; SGPT = serum glutamyl pyruvic transaminase; SU = sulfonylurea; TG = triglycerides; TZD = thiazolidinedione; VHA = Veterans Health Administration; WHO = World Health Organization |Abbreviations for Appendix G - Table 7: AA= African American; C= Caucasian; H=Hispanic; Kg=kilogram; Met=Metformin; NR=Not reported; Repa=Repaglinide; Rosi=Rosiglitazone; Sita=Sitagliptin; SU=Sulfonylurea | Abbreviations for Appendix G - Table 10: ACEI = angiotensin-converting enzyme inhibitors; ALT = alanine aminotransferase; AST = asparate aminotransferase; BID = twice a day; BMI = body mass index; CAD = coronary artery disease; CHF = congestive heart failure; CK = creatine kinase; CVD = cardiovascular diseases; DBP = diastolic blood pressure; DKA = diabetic ketoacidosis; DM = diabetes mellitus; FBG = fasting blood glucose; FPG = fasting plasma glucose; GFR = glomerular filtration rate; GI = gastrointestinal; HbA1c = hemoglobin A1c; HONK = hyper osmolar non ketotic; HTN = hypertension; ICD = International classification disease;kg/m2 = kilograms per meters squared; LDL = low density lipoprotein; LVEF = left ventricular ejection fraction; mg/d = milligrams per day; mg/dl = milligrams/deciliter; MHS = Military health system; mmHg = millimeters of mercury; mmol = millimoles; mmol/L = millimoles per liter; NA = not applicable; NPH = neutral protamine Hagedorn; NR = not reported; NSAID = nonsteroidal antiinflammatory drug; NYHA = New York Health Association; OAD = oral antidiabetic; OAM = oral antihyperglycemic medications; PPAR-G = peroxisome proliferator-activated receptors-gamma; PPG = postprandial glucose; QD = once a day; RCT = randomized controlled trial; SBP = systolic blood pressure; SC = subcutaneous; SGOT = serum glutamyl oxaloacetic transaminase; SGPT = serum glutamyl pyruvic transaminase; SU = sulfonylurea; TG = triglycerides; TZD = thiazolidinedione; U/kg = unit per kilogram; y = years |Abbreviations for Appendix G - Table 11: AA=African American; C=Caucasian; H=Hispanic; kg=kilogram; NR=not reported; O = other|
Funding Source
The Agency for Healthcare Research and Quality (AHRQ)

Key Questions

1. Key Question 1 - Study design and population characteristics of studies reporting on the comparative effectiveness of diabetes medications on intermediate and long-term outcomes, and adverse events
2. Key Question 2 - Study quality of randomized controlled trials reporting on the comparative effectiveness and safety of diabetes medications
3. Key Question 3 - Study quality of observational studies reporting on the comparative safety of diabetes medications
4. Key Question 4 - Summary of studies reporting on more than one study

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy.2005
The short-term effect of a switch from glibenclamide to metformin on blood pressure and microalbuminuria in patients with type 2 diabetes mellitus.-- Not Found --
Evaluation of adverse events of oral antihyperglycemic monotherapy experienced by a geriatric population in a real-world setting: a retrospective cohort analysis.2008
Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes.2010
Rosiglitazone/metformin fixed-dose combination compared with uptitrated metformin alone in type 2 diabetes mellitus: a 24-week, multicenter, randomized, double-blind, parallel-group study.2005
Rosiglitazone reduces urinary albumin excretion in type II diabetes.2003
Rosiglitazone reduces microalbuminuria and blood pressure independently of glycemia in type 2 diabetes patients with microalbuminuria.2006
Long-term effects on lipids and lipoproteins of pioglitazone versus gliclazide addition to metformin and pioglitazone versus metformin addition to sulphonylurea in the treatment of type 2 diabetes.2005
Glyburide/metformin combination product is safe and efficacious in patients with type 2 diabetes failing sulphonylurea therapy.2002
Rapid identification of myocardial infarction risk associated with diabetes medications using electronic medical records.2010
One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial.2009
One year comparative trial of metformin and glipizide in type 2 diabetes mellitus.-- Not Found --
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.2006
Improved glycaemic control by addition of glimepiride to metformin monotherapy in type 2 diabetic patients.2001
Effect of glyburide-metformin combination tablet in patients with type 2 diabetes.2007
Effects of pioglitazone in combination with metformin or a sulfonylurea compared to a fixed-dose combination of metformin and glibenclamide in patients with type 2 diabetes.2007
The effect of pioglitazone as add-on therapy to metformin or sulphonylurea compared to a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia.2008
Thiazolidinediones and cardiovascular events in patients with type 2 diabetes mellitus: a retrospective cohort study of over 473,000 patients using the National Health Insurance database in Taiwan.2009
The influence of glucose-lowering therapies on cancer risk in type 2 diabetes.2009
A randomized controlled trial examining combinations of repaglinide, metformin and NPH insulin.2007
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.1995
The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone.2009
Effects of exenatide plus rosiglitazone on beta-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin.2010
Metabolic variations with oral antidiabetic drugs in patients with Type 2 diabetes: comparison between glimepiride and metformin.2004
Antithrombotic effects of rosiglitazone-metformin versus glimepiride-metformin combination therapy in patients with type 2 diabetes mellitus and metabolic syndrome.2005
Long-term effect of glimepiride and rosiglitazone on non-conventional cardiovascular risk factors in metformin-treated patients affected by metabolic syndrome: a randomized, double-blind clinical trial.-- Not Found --
Direct comparison among oral hypoglycemic agents and their association with insulin resistance evaluated by euglycemic hyperinsulinemic clamp: the 60's study.2009
Exenatide versus glibenclamide in patients with diabetes.2010
Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors.2003
Comparison of glycaemic control and cardiovascular risk profile in patients with type 2 diabetes during treatment with either repaglinide or metformin.2003
Long-term effects of glimepiride or rosiglitazone in combination with metformin on blood pressure control in type 2 diabetic patients affected by the metabolic syndrome: a 12-month, double-blind, randomized clinical trial.2005
Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial.
Effects of nateglinide and glibenclamide on prothrombotic factors in naïve type 2 diabetic patients treated with metformin: a 1-year, double-blind, randomized clinical trial.2007
Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metformin.2009
Evaluation of the repaglinide efficiency in comparison to the glimepiride in the type 2 diabetes patients poorly regulated by the metmorfine administration.2009
Thiazolidinediones and fractures in men and women.2009
Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. The Pioglitazone 027 Study Group.2000
Improved clinical outcomes associated with metformin in patients with diabetes and heart failure.2005
Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin.2006
Effect on glycemic control of the addition of 2.5 mg glipizide GITS to metformin in patients with T2DM.2005
Antihyperglycemic treatment in diabetics with coronary disease: increased metformin-associated mortality over a 5-year follow-up.1999
Oral antidiabetic treatment in patients with coronary disease: time-related increased mortality on combined glyburide/metformin therapy over a 7.7-year follow-up.2001
Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial.2000
Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes.2003
Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy.2006
Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial.2009
Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes.
PRESERVE-beta: two-year efficacy and safety of initial combination therapy with nateglinide or glyburide plus metformin.2005
A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.2005
Multicenter, randomized, double-masked, parallel-group assessment of simultaneous glipizide/metformin as second-line pharmacologic treatment for patients with type 2 diabetes mellitus that is inadequately controlled by a sulfonylurea.2003
Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes.2007
Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2 diabetes.-- Not Found --
Mortality in type 2 diabetic subjects prescribed metformin and sulphonylurea drugs in combination: cohort study.-- Not Found --
Pioglitazone treatment in type 2 diabetes mellitus when combined with portion control diet modifies the metabolic syndrome.2009
Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes.2002
Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone.2004
Comparison of fixed-dose rosiglitazone/metformin combination therapy with sulphonylurea plus metformin in overweight individuals with Type 2 diabetes inadequately controlled on metformin alone.2008
One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes.
Glycemic control and treatment failure with pioglitazone versus glibenclamide in type 2 diabetes mellitus: a 42-month, open-label, observational, primary care study.2006
A one-year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes.2007
Effects of metformin and glibenclamide alone and in combination on serum lipids and lipoproteins in patients with non-insulin-dependent diabetes mellitus.
Comparative efficacy of metformin and glibenclamide in patients with non-insulin-dependent diabetes mellitus.1991
Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study.1994
Rosiglitazone RECORD study: glucose control outcomes at 18 months.2007
Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial.2009
Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes.2000
Efficacy and tolerability of initial combination therapy with nateglinide and metformin in treatment-naïve patients with type 2 diabetes.2004
Effectiveness and side effects of thiazolidinediones for type 2 diabetes: real-life experience from a tertiary hospital.2004
Metabolic effects of rosiglitazone and metformin in Greek patients with recently diagnosed type 2 diabetes.-- Not Found --
Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial.2009
Long-term safety of pioglitazone versus glyburide in patients with recently diagnosed type 2 diabetes mellitus.2006
Safety and efficay of repaglinide compared with glibenclamide in the management of type 2 diabetic Pakistani patients.
Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes.2002
Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes.
Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes.2003
Pioglitazone compared with metformin increases pericardial fat volume in patients with type 2 diabetes mellitus.2010
Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone.2004
Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study.
Impact of oral antihyperglycemic therapy on all-cause mortality among patients with diabetes in the Veterans Health Administration.2007
Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT).2008
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.2006
Efficacy and safety of therapy with metformin plus pioglitazone in the treatment of patients with type 2 diabetes: a double-blind, placebo-controlled, clinical trial.
Pioglitazone initiation and subsequent hospitalization for congestive heart failure.
Comparative study of low-dose pioglitazone or metformin treatment in Japanese diabetic patients with metabolic syndrome.2009
A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone.2002
Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin-18 is an independent factor for the improvement of homeostasis model assessment-beta in type 2 diabetes mellitus.2007
Effect of rosiglitazone, metformin and medical nutrition treatment on arterial stiffness, serum MMP-9 and MCP-1 levels in drug naive type 2 diabetic patients.2009
Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial.2010
Biphasic insulin aspart 30 plus metformin: an effective combination in type 2 diabetes.2006
A comparison of repaglinide and glibenclamide in the treatment of type 2 diabetic patients previously treated with sulphonylureas.1999
Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study.2005
Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes.2004
Efficacy and safety of Rosiglitazone as monotherapy or in combination with metformin in primary care settings
Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial.2007
Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.2001
Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial.
Therapy after single oral agent failure: adding a second oral agent or an insulin mixture?2003
Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy.
Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with Type 2 diabetes.2005
Vertebral fractures in males with type 2 diabetes treated with rosiglitazone.2009
Repaglinide versus glyburide: a one-year comparison trial.1999
Improved glycaemic control with metformin-glibenclamide combined tablet therapy (Glucovance) in Type 2 diabetic patients inadequately controlled on metformin.2002
Nateglinide improves glycaemic control when added to metformin monotherapy: results of a randomized trial with type 2 diabetes patients.2002
Antidiabetic drugs and heart failure risk in patients with type 2 diabetes in the U.K. primary care setting.2005
Coronary heart disease outcomes in patients receiving antidiabetic agents.2007
The risk of heart failure in patients with type 2 diabetes treated with oral agent monotherapy.2008
Effect of combined secretagogue/biguanide treatment on mortality in type 2 diabetic patients with and without ischemic heart disease.2008
Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.1999
Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-1 and albumin excretion in diabetes patients.-- Not Found --
Effect of pioglitazone on carotid intima-media thickness and arterial stiffness in type 2 diabetic nephropathy patients.2004
Effect of pioglitazone on urinary liver-type fatty acid-binding protein concentrations in diabetes patients with microalbuminuria.-- Not Found --
Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes.
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.2007
Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study.2009
The incidence of congestive heart failure associated with antidiabetic therapies.-- Not Found --
The risk of developing coronary artery disease or congestive heart failure, and overall mortality, in type 2 diabetic patients receiving rosiglitazone, pioglitazone, metformin, or sulfonylureas: a retrospective analysis.2009
Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes.2003
Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM.2009
Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study.2005
Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial.2010
Effect of pioglitazone on metabolic syndrome risk factors: results of double-blind, multicenter, randomized clinical trials.
Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.2005
Use of glimepiride and insulin sensitizers in the treatment of type 2 diabetes--a study in Indians.2004
Combination therapy for type 2 diabetes: repaglinide plus rosiglitazone.2004
Basal insulin or premix analogue therapy in type 2 diabetes patients.2007
Twice-daily dosing of a repaglinide/metformin fixed-dose combination tablet provides glycaemic control comparable to rosiglitazone/metformin tablet.2009
Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes.
Effects of colesevelam, rosiglitazone, or sitagliptin on glycemic control and lipid profile in patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy.-- Not Found --
Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison.2007
Rosiglitazone is effective and well-tolerated in a range of therapeutic regimens during daily practice in patients with type 2 diabetes.2006
Initial treatment with rosiglitazone/metformin fixed-dose combination therapy compared with monotherapy with either rosiglitazone or metformin in patients with uncontrolled type 2 diabetes.2006
Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.
Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naïve elderly patients with type 2 diabetes.2008
Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes.2007
Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.2008
Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study.2010
Efficacy and safety of the once-daily human GLP-1 analogue, liraglutide, vs glibenclamide monotherapy in Japanese patients with type 2 diabetes.2010
2-year effects of pioglitazone add-on to sulfonylurea or metformin on oral glucose tolerance in patients with type 2 diabetes.2008
Dose-response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study.2006
Rosiglitazone, but not glyburide, reduces circulating proinsulin and the proinsulin:insulin ratio in type 2 diabetes.2004
A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes.2002
Effect of metformin plus roziglitazone compared with metformin alone on glycaemic control in well-controlled Type 2 diabetes.2006
Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.2004
Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes mellitus: A multicenter, randomized, double-blind, parallel-group trial.2004
Effects of pioglitazone hydrochloride on Japanese patients with type 2 diabetes mellitus.2007
Liver safety in patients with type 2 diabetes treated with pioglitazone: results from a 3-year, randomized, comparator-controlled study in the US.2009
Combination treatment with metformin and glibenclamide versus single-drug therapies in type 2 diabetes mellitus: a randomized, double-blind, comparative study.2003
Effects of rosiglitazone on plasma brain natriuretic peptide levels and myocardial performance index in patients with type 2 diabetes mellitus.2007
Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group.1999
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database.
Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial.2006
Effects of nateglinide and glibenclamide on postprandial lipid and glucose metabolism in type 2 diabetes.-- Not Found --
Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus.2009
Effect of pioglitazone and rosiglitazone on mediators of endothelial dysfunction, markers of angiogenesis and inflammatory cytokines in type-2 diabetes.2009
Effects of rosiglitazone added to submaximal doses of metformin compared with dose escalation of metformin in type 2 diabetes: the EMPIRE Study.2005
Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study.
Effects of a new oral hypoglycaemic agent, repaglinide, on metabolic control in sulphonylurea-treated patients with NIDDM.1993
A 1-year multicenter randomized double-blind comparison of repaglinide and glyburide for the treatment of type 2 diabetes. Dutch and German Repaglinide Study Group.1999
Hypoglycemia in Type 2 diabetic patients randomized to and maintained on monotherapy with diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis: UKPDS73.-- Not Found --
Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes.
Efffect of addition of low-dose rosiglitazone to sulphonylurea therapy on glycemic control in type 2 diabetic patients.2003
The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus.2008
Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects.2003
Blood pressure control and inflammatory markers in type 2 diabetic patients treated with pioglitazone or rosiglitazone and metformin.2007
Effects of pretreatment with low-dose metformin on metabolic parameters and weight gain by pioglitazone in Japanese patients with type 2 diabetes.2008
Pioglitazone in a subgroup of patients with type 2 diabetes meeting the criteria for metabolic syndrome.2005
Repaglinide versus glibenclamide treatment of Type 2 diabetes during Ramadan fasting.2002
Comparison of pioglitazone and metformin efficacy using homeostasis model assessment.2004
Cardiovascular effects of treatment of type 2 diabetes with pioglitazone, metformin and gliclazide.2004
Effects of pioglitazone on the components of diabetic dyslipidaemia: results of double-blind, multicentre, randomised studies.2004
Pioglitazone plus a sulphonylurea or metformin is associated with increased lipoprotein particle size in patients with type 2 diabetes.2004
Changes in liver tests during 1-year treatment of patients with Type 2 diabetes with pioglitazone, metformin or gliclazide.2005
Safety and tolerability of pioglitazone, metformin, and gliclazide in the treatment of type 2 diabetes.2005
Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes.2005
Comparison of effect of pioglitazone with metformin or sulfonylurea (monotherapy and combination therapy) on postload glycemia and composite insulin sensitivity index during an oral glucose tolerance test in patients with type 2 diabetes.
Combination therapy with pioglitazone plus metformin or sulfonylurea in patients with Type 2 diabetes: influence of prior antidiabetic drug regimen.-- Not Found --

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