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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

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

BACKGROUND: Alogliptin is a new dipeptidyl peptidase (DPP-4) inhibitor, which is under investigation for treatment of type 2 diabetes either alone or in combination with other antidiabetic drugs. The aim of this meta-analysis was to assess the efficacy and tolerability of alogliptin in patients with type 2 diabetes.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

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

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

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

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

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

The objective of this review was to summarize and critically appraise the evidence regarding the clinical effectiveness and harms of combination use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) analogues with insulin. The following research questions were assessed:

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

Version: July 2013

Evidence-informed recommendations were developed by the Canadian Drug Expert Committee (CDEC) to address the following policy questions:

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

Version: July 2013

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

The study found evidence to suggest that integrated continuous glucose monitoring insulin pump therapy systems are more clinically effective in patients with type 1 diabetes than stand-alone treatments. However, based on the evidence available, these integrated systems are unlikely to be cost-effective in comparison with stand-alone insulin delivery and monitoring. Further research on the clinical effectiveness and cost-effectiveness of these integrated systems in different populations is warranted.

Health Technology Assessment - NIHR Journals Library.

Version: February 2016

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

Sodium-glucose co-transport 2 (SGLT-2) inhibitors are a new class of drugs used to treat type-2 diabetes (T2DM). They exert antihyperglycemic action by blocking the renal reabsorption of glucose, leading to increased urinary glucose excretion. In healthy individuals, the kidney filters up to 180g of glucose every day, which is almost entirely reabsorbed into the blood in the proximal convoluted tubule through the mediation of SGLT-1 and SGLT-2, with the latter reabsorbing the majority (80% to 90%). Based on their mechanism of action and observations from clinical trials, the SGLT-2 inhibitors have demonstrated the potential to reduce the risk of cardiovascular events in addition to reducing blood glucose levels. By inhibiting renal reabsorption of glucose, they lower blood glucose to clinically significant levels, increase the potential for weight loss through calorie reduction, and increase water content of urine by osmotic diuresis to potentially reduce blood pressure.

Rapid Response Report: Summary with Critical Appraisal - Canadian Agency for Drugs and Technologies in Health.

Version: November 5, 2015

Metformin is a biguanide oral hypoglycemic used primarily for treating type 2 diabetes mellitus (T2D). Evidence suggests that, in addition to improving glycemic control, metformin is associated with improved all-cause and cardiovascular mortality and decreased risk of some cancers. However, clinicians have been advised by the U.S. Food and Drug Administration (FDA) to exercise caution in prescribing metformin to individuals with chronic kidney disease (CKD), unstable congestive heart failure (CHF), chronic liver disease (CLD), and older age due to perceived risk of side effects, including lactic acidosis (LA).

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

Version: September 2016

PURPOSE: Although recent reports suggest an association between saxagliptin and an increased risk of admissions for heart failure, it is not clear whether dipeptidyl peptidase IV (DPP-IV) inhibition contributes to heart failure in high-risk patients. The purpose of this research is to understand heart failure risk among high-risk patients with type 2 diabetes.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

OBJECTIVE: To compare the safety and efficacy of the dipeptidylpeptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes and inadequate glycemic control.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

OBJECTIVE: The use of dipeptidyl-peptidase 4 (DPP4) inhibitors and glucagon like peptide 1 (GLP1) analogues for the treatment of diabetic mellitus (DM) type 2 is growing. Currently some of these agents have been approved in combination with insulin.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

AIM: Some observational studies reporting an increased risk of pancreatitis in association with Dipeptidyl Peptidase-4 inhibitors (DPP4i) have raised concerns on the overall safety of this class. Aim of the present meta-analysis is the systematic collection of information on pancreatitis in randomized clinical trials with DPP4i.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

BACKGROUND & AIMS: Recently, the SAVOR TIMI-53 (Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus--Thrombolysis in Myocardial Infarction-53) reported a significant increase in the risk of hospitalizations for heart failure in patients treated with saxagliptin in comparison with placebo. Aim of the present meta-analysis is the systematic collection and synthesis of information on treatment-emergent cases of acute heart failure described in randomized clinical trials with DPP4.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Systematic Reviews in PubMed

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