Pioglitazone for Type 2 Diabetes Mellitus and Pre-Diabetes: A Review of Safety [Internet]
Bibliographic record
Abstract
Diabetes mellitus is a group of metabolic disorders that result from deficiencies in insulin secretion, sensitivity, or both. Type 2 diabetes mellitus ranges from predominant insulin resistance with relative insulin secretory deficiency, to insulin resistance with a predominant insulin secretory deficiency as the disease progresses.– There are several risk factors for type 2 diabetes, including a history of pre-diabetes, usually defined as having impaired fasting glucose (6.1 to 6.9 mmol/L), impaired glucose tolerance (noted by an oral glucose tolerance test results of 7.8 to 11 mmol/L), or an elevated glycated hemoglobin A1c level (6% to 6.4%).In 2017, it was estimated there were 123,085 Canadians (95% confidence interval [CI], 109,119 to 137,118) newly diagnosed with type 2 diabetes, raising the national burden of disease to an estimated 2,553,158 (95% CI, 2,295,152 to 2,857,046) prevalent cases. Furthermore, it was estimated that 2.12% of total Canadian deaths (95% CI, 2.0% to 2.25%) in 2017 were attributable to type 2 diabetes. This translates to an estimated 83,603 years of life lost (95% CI, 76,847 to 90,036) for 2017.The goals of therapy in type 2 diabetes are aimed at achieving stringent glycemic control within the normal range as early as possible. In addition to diet and lifestyle measures, several classes of antidiabetic agents are approved in Canada: insulins, sulphonylureas (SUs), α-glucosidase inhibitors, biguanides, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides (MEGs), thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and a combination of these may often be necessary for optimal treatment.–, This report will focus on a particular drug of the TZD class, pioglitazone (PIO), which is often considered as a therapeutic option when glycemic targets are not achieved with first-line drugs, such as metformin. PIO works by binding to the peroxisome proliferator-activated receptor-γ, which is primarily located on adipose and vascular cells, increasing their insulin sensitivity.In addition to its hypoglycemic effect, PIO has been shown to have favourable effects on reducing major adverse cardiovascular events (e.g., all-cause mortality, non-fatal myocardial infarction [MI], stroke)., Nevertheless, and as is the case with any drug therapy, the benefits associated with PIO ought to be weighed against possible risks to the patient. Because of previously reported concerns about adverse events (AEs) such as bladder cancer,– heart failure (HF),,, edema,,, fractures,, weight gain, and ovulation in anovulatory women, there remains uncertainty around the overall safety profile of PIO.Previous CADTH reports on this topic include a 2010 comparison of the safety of PIO and rosiglitazone (ROS) for patients with type 2 diabetes. The objective of the present report is to investigate the clinical evidence regarding the safety of PIO for patients with pre-diabetes or type 2 diabetes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".