Comparative effectiveness and safety of insulin reference biologics versus biosimilars for types 1 and 2 diabetes mellitus: Protocol for a systematic review of real-world studies
Bibliographic record
Abstract
INTRODUCTION: Diabetes mellitus is characterized by insulin deficiency or resistance. The two main types of diabetes mellitus are type 1 (T1DM) and type 2 (T2DM). Insulin is the mainstay of therapy for T1DM and often the last-line therapy for T2DM. Biosimilar insulins are cost-saving alternatives to reference products that may improve access for patients and sustainability for healthcare systems. Despite supporting evidence from randomized controlled trials, biosimilar insulin uptake is poor, and real-world evidence of their safety and effectiveness is limited. OBJECTIVE: Our objective is to compare the real-world effectiveness and safety of insulin biosimilars versus reference products in adults with diabetes mellitus. ELIGIBILITY CRITERIA: We will include observational studies and open-label pragmatic randomized controlled trials. We will exclude other randomized controlled trials, literature reviews, meta-analyses, case series, case reports, study protocols, opinion pieces, and conference abstracts. Our primary effectiveness outcome will be glycated hemoglobin (HbA1c) and our primary safety outcome will be hypoglycemia. Our secondary outcomes will include fasting plasma glucose; time in range; microvascular complications; health-related quality of life; physician visits, emergency department visits, and hospital admissions for hypoglycemia, hyperglycemia, and diabetic ketoacidosis; weight gain; immunogenicity; injection site reactions; and incident cancers. METHODS: The search strategy combines three key concepts: diabetes, insulin, and biosimilars. We will conduct a structured search in MEDLINE, EMBASE, and International Pharmaceutical Abstracts. We will also search in grey literature databases, targeted websites, and the Google search engine. Finally, we will scan forward and backward citations. Articles will be screened, extracted, and appraised independently by two reviewers. Data will be descriptively summarized. DISCUSSION: Our systematic review of the real-world evidence on biosimilar insulins can help support clinical and policy decisions that impact the care of patients with T1DM or T2DM.
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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 | 0.069 | 0.107 |
| Meta-epidemiology (narrow) | 0.007 | 0.004 |
| Meta-epidemiology (broad) | 0.029 | 0.028 |
| Bibliometrics | 0.015 | 0.016 |
| Science and technology studies | 0.003 | 0.004 |
| Scholarly communication | 0.008 | 0.007 |
| Open science | 0.005 | 0.006 |
| Research integrity | 0.008 | 0.005 |
| Insufficient payload (model declined to judge) | 0.034 | 0.004 |
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".