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Medicines for Type 2 Diabetes: A Review of the Research for Adults

This summary covers the research on the benefits and possible side effects of medicines to lower or control your blood sugar. It will help you talk with your doctor or other health care professional to decide which medicines are best for you.

Comparative Effectiveness Review Summary Guides for Consumers [Internet] - Agency for Healthcare Research and Quality (US).

Version: June 30, 2011

Drug Class Review: Newer Diabetes Medications, TZDs, and Combinations: Final Original Report [Internet]

To compare the effectiveness and adverse event profiles of amylin agonists, DPP-4 inhibitors, incretin mimetics, TZDs, and certain combination products for people with type 2 diabetes and for people with type 1 diabetes for pramlintide only.

Drug Class Reviews - Oregon Health & Science University.

Version: February 2011
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Drugs for preventing recurrent stroke and other vascular events in people who have already had a stroke or transient ischaemic attack

Question: We wanted to evaluate the effectiveness and safety of peroxisome proliferator‐activated receptor gamma (PPAR‐γ) agonists (e.g. pioglitazone or rosiglitazone) versus placebo in the secondary prevention of stroke and related vascular events for people who have already had a stroke or transient ischaemic attack.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2015

Glucose‐lowering agents for treating pre‐existing or new‐onset diabetes in kidney transplant recipients

Kidney transplantation is often complicated by worsening or new‐onset diabetes. The safety and effectiveness of drugs used to lower glucose in this setting is largely not known.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: February 27, 2017

Third-Line Pharmacotherapy for Type 2 Diabetes — Update [Internet]

The objective of this review was to update the systematic review and network meta-analysis of third-line therapies for type 2 diabetes.

CADTH Optimal Use Report - Canadian Agency for Drugs and Technologies in Health.

Version: July 2013
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Canagliflozin (Invokana) for Type 2 Diabetes Mellitus [Internet]

Canagliflozin is the first sodium-glucose cotransporter-2 (SGLT2) inhibitor to be approved for use in Canada. Canagliflozin is indicated for patients with type 2 diabetes to improve glycemic control as monotherapy or in combination with metformin; a sulfonylurea; metformin and a sulfonylurea; metformin and pioglitazone; or insulin (with or without metformin) when these drugs do not provide adequate glycemic control. The recommended starting dose is 100 mg once daily. A dose of 300 mg once daily may be considered for patients who have tolerated a dose of 100 mg once daily and who need tighter glycemic control, provided they have an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m2 and have a low risk of adverse reactions associated with reduced intravascular volume. Canagliflozin is contraindicated in renally impaired patients who have an eGFR of less than 45 mL/min/1.73 m2, have end-stage renal disease, or are on dialysis.

Common Drug Review - Canadian Agency for Drugs and Technologies in Health.

Version: September 2015
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Alogliptin Plus Metformin (Kazano) for Type 2 Diabetes Mellitus [Internet]

Diabetes is a chronic, metabolic disease with significant health impacts on individuals and societies. The prevalence of diabetes in Canada was 6.8% (2.4 million Canadians) in 2009 and is expected to rise to 3.7 million people by 2019. Ninety per cent of people with diabetes have type 2 diabetes mellitus (T2DM). T2DM is characterized by increased hepatic glucose output, reduced insulin secretion, and insulin resistance. People with diabetes are at risk of microvascular complications such as diabetic nephropathy and retinopathy, macrovascular complications such as cardiovascular disease, and premature mortality. Improved glycemic control reduces the risk of microvascular complications, and possibly of macrovascular complications. Current guideline recommendations specify a target for glycated hemoglobin (A1C) of 7% or less for most patients with T2DM.

Common Drug Review - Canadian Agency for Drugs and Technologies in Health.

Version: August 2015
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Mapping the Evidence: Sex Effects in High-Impact Conditions for Women Veterans – Depression, Diabetes, and Chronic Pain [Internet]

Women are entering the military at unprecedented rates and comprise a rapidly increasing segment of Veterans Health Administration (VHA) enrollees. In response, the VHA Women's Health Service requested an evidence map to (1) identify effective interventions in women, (2) better understand sex differences in intervention effects for high-impact medical conditions, and (3) identify gaps in evidence about the efficacy of interventions in women.

Evidence-based Synthesis Program - Department of Veterans Affairs (US).

Version: September 2015
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Second-Line Pharmacotherapy for Type 2 Diabetes — Update [Internet]

The objective of this study was to perform an update of CADTH’s original systematic review, network meta-analysis, and cost-effectiveness analysis of second-line diabetes pharmacotherapy. The research questions that were addressed in the update were the same as in the original review:

CADTH Optimal Use Report - Canadian Agency for Drugs and Technologies in Health.

Version: July 2013
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Second- and Third-Line Pharmacotherapy for Type 2 Diabetes — Update of CADTH 2010 Reviews — Project Protocol [Internet]

In August 2010, the Canadian Agency for Drugs and Technologies in Health (CADTH) published an Optimal Therapy Report which assessed the clinical and cost-effectiveness of second-line therapies for patients with type 2 diabetes inadequately controlled on metformin. The results from the CADTH review indicated that there were no apparent differences in efficacy across drug classes, and that sulfonylureas were the most cost-effective treatment option. Based on these analyses, the Canadian Optimal Medication Prescribing and Utilization Service (COMPUS) Expert Review Committee (CERC) recommended that most patients requiring a second treatment after metformin should be prescribed a sulfonylurea. CADTH followed this report with a Therapeutic Review which examined the evidence for third-line treatment options for adults with type 2 diabetes inadequately controlled on metformin and a sulfonylurea. The results demonstrated that insulins (basal, biphasic, bolus), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, and thiazolidinediones (TZDs) all produced statistically significant reductions in hemoglobin A1C in combination with metformin and a sulphonylurea. Meglitinides and alpha-glucosidase inhibitors, however, did not. The addition of insulin neutral protamine Hagedorn (NPH) to metformin plus a sulfonylurea was associated with the most favourable cost-effectiveness estimates. CADTH’s Therapeutic Review Panel (TRP) recommended that, for most adults with type 2 diabetes inadequately controlled on metformin and a sulfonylurea, insulin NPH should be added as the third-line agent. Long-acting insulin analogues at prices similar to insulin NPH were also considered an option for patients inadequately controlled on metformin and a sulfonylurea.

CADTH Optimal Use Report - Canadian Agency for Drugs and Technologies in Health.

Version: November 2012
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Drug Class Review: Thiazolidinediones: Final Report Update 1 [Internet]

There are 2 thiazolidinediones approved for prescription use in the United States, rosiglitazone maleate (Avandia™) and pioglitazone hydrochloride (Actos®). Both drugs are approved by the United States Food and Drug Administration for use in adults for the treatment of type 2 diabetes, either as monotherapy or in combination with insulin, metformin, or sulfonylurea when diet, exercise, and a single agent does not result in adequate glycemic control. Neither drug is currently approved for use in prediabetes or the metabolic syndrome. The objective of this review was to compare thiazolidinediones in the treatment of type 2 diabetes, prediabetes, and the metabolic syndrome.

Drug Class Reviews - Oregon Health & Science University.

Version: August 2008
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Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Although dapagliflozin, canagliflozin and empagliflozin improve glycaemic control, as monotherapy they are not cost-effective compared with gliclazide or pioglitazone, but may be against sitagliptin.

Health Technology Assessment - NIHR Journals Library.

Version: January 2017
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Change Score or Followup Score? An Empirical Evaluation of the Impact of Choice of Mean Difference Estimates [Internet]

In randomized controlled clinical trials, continuous outcomes are typically measured at both baseline and followup time points, and mean difference is analyzed as the effect measure. There are multiple ways to estimate the mean difference: using the change score from the baseline, using the followup scores, or estimating the mean difference using the analysis of covariance (ANCOVA) model. Use of the ANCOVA model is generally preferable to using the change scores from the baseline or using the followup scores. When the baseline scores are imbalanced, using either the change score from the baseline or the followup scores would produce biased effect estimates of mean difference, while the ANCOVA model provides the least biased estimates. Nonetheless, individual studies often report results incompletely, and investigators have to summarize results across studies that are not optimally reported. The impact of using the change versus the followup score on meta-analysis has not been well studied.

Research White Paper - Agency for Healthcare Research and Quality (US).

Version: April 2015
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Alogliptin (Nesina) for Type 2 Diabetes Mellitus [Internet]

Diabetes is a chronic metabolic disease with significant health impacts on individuals and societies. The prevalence of diabetes in Canada was 6.8% (2.4 million Canadians) in 2009 and is expected to rise to 3.7 million people by 2019. Ninety per cent of people with diabetes have type 2 diabetes mellitus, which is characterized by increased hepatic glucose output, reduced insulin secretion, and insulin resistance. People with diabetes are at risk of microvascular complications such as diabetic nephropathy and retinopathy, macrovascular complications such as cardiovascular disease, and premature mortality. Improved glycemic control reduces the risk of microvascular complications and possibly of macrovascular complications. Current guideline recommendations specify a target for glycated hemoglobin (A1C) of 7% or less for most patients with type 2 diabetes.

Common Drug Review - Canadian Agency for Drugs and Technologies in Health.

Version: August 2015
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Insulin Sensitisers in the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review

Non-alcoholic fatty liver disease (NAFLD) is closely linked with obesity and the prevalence of NAFLD is about 17% to 33% in the Western world. There is a strong association of NAFLD with insulin resistance and, hence, insulin sensitisers have been tried. This systematic review examined the clinical effectiveness of insulin sensitisers in patients with NAFLD, to help decide whether or not a trial or trials of the insulin sensitisers was necessary and also to explore whether or not non-invasive alternatives to liver biopsy were available that could be used in a large trial of the insulin sensitisers.

Health Technology Assessment - NIHR Journals Library.

Version: November 2011
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Insulin sensitisers in the treatment of non-alcoholic fatty liver disease: a systematic review.

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease, ranging from an increased fat content in the liver (steatosis) to inflammatory change (non-alcoholic steatohepatitis – NASH), and potentially to fibrosis and cirrhosis. By definition, it is seen in people whose alcohol intake is not increased (such as < 10 g a day for women, < 20 g a day for men).

NIHR Health Technology Assessment programme: Executive Summaries - NIHR Journals Library.

Version: 2011

Combinations of insulin and oral glucose‐lowering drugs for people with type 2 diabetes on insulin treatment

Many guidelines on type 2 diabetes recommend a glycosylated haemoglobin A1c (HbA1c) level below 7%. HbA1c levels in the blood express glucose or glycaemic control over a longer time period (two to three months). During the course of type 2 diabetes it will get more difficult to reach these levels with 'lifestyle' modification (diet, exercise or both) and oral glucose‐lowering agents alone. Finally, a substantial number of people will need insulin therapy for better glycaemic control. Insulin therapy can be initiated as insulin alone, called monotherapy (which means that oral glucose‐lowering medication will be stopped) or in combination with oral glucose‐lowering agents. In the former case, oral blood glucose‐lowering agents can be added at a later stage, if insulin monotherapy fails to achieve a good HbA1c level. Hypoglycaemia and weight gain are the most common and well known side effects of insulin therapy. Adding oral agents to insulin could reduce the required insulin dose and thus decrease these insulin‐related side effects. However, there could be other side effects specific to the various oral blood glucose‐lowering drugs.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2016

Glucagon‐like peptide analogues for type 2 diabetes

Glucagon‐like peptide analogues or agonists are a new kind of drug in the treatment of type 2 diabetes that are given by injection under the skin. They regulate glucose levels by stimulating glucose‐dependent insulin secretion and biosynthesis, and by suppressing glucagon secretion, delaying gastric emptying and promoting satiety.  Various glucagon‐like peptide‐1 agonists are in use or in the licensing process, including exenatide, liraglutide, albiglutide, taspoglutide, lixisenatide and LY2189265.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2013

Diabetes Medications for Adults With Type 2 Diabetes: An Update [Internet]

To evaluate the comparative effectiveness and safety of monotherapy and metformin-based combination therapy for type 2 diabetes.

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US).

Version: April 2016
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Non-Alcoholic Fatty Liver Disease: Assessment and Management

This guideline covers identifying, diagnosing and assessing disease severity in adults, children and young people with non-alcoholic fatty liver disease (NAFLD). It also covers both pharmacological and non-pharmacological treatments, disease monitoring and the risk of extra-hepatic conditions associated with NAFLD.

NICE Guideline - National Guideline Centre (UK).

Version: July 2016
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