HbA1c: Glycated Hemoglobin, or HbA1c, provides the best, long term, gauge of blood glucose control. A diabetic patient may have a HbA1c of 75 mmol/mol (9%), whilst a normal HbA1c is below 42 mmol/mol (6%). Lower levels are better, and a common treatment goal is to reduce HbA1c to below 53 mmol/mol (7%).

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All antihyperglycemic drugs reduce HbA1c, with reductions from 6 mmol/mol with the least efficacious drugs to 22 mmol/mol with the most efficacious (best) drugs.

Weight: In addition to blood glucose control, the different drugs may increase or decrease body weight. Since weight management is often important for patients, drugs that reduce weight are preferable.

Hypoglycemia: One of the main risks with antihyperglycemic drugs is hypoglycemia. Hypoglycemia, also known as low blood sugar, is when blood sugar decreases to below normal levels. This may result in a variety of symptoms including clumsiness, trouble talking, confusion, loss of consciousness, seizures, or death.

Results: The treatment effects illustrated below are based on 6 months treatment, for drug naive patients with a baseline HbA1c of 65 mmol/mol, and baseline weight of 90 kg. All treatment differences are versus placebo. For hypoglycemia, we report the relative risk (risk on drug / risk on placebo).

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All treatment effects and treatment differences are dependent on multiple factors, including the duration of the study, the patient population and the baseline HbA1c. The mathematical models we developed appropriately adjust for these important factors (study differences), ensuring we truly compare 'apples with apples'. In addition, we can generate predictions for any combination of these factors, for any choice of comparator (i.e. instead of placebo, we could choose sitagliptin 100 mg, or semaglutide 1 mg).

Drug Class: There are many ways antihyperglycemic drugs interact with the body to improve glycemic control. Drugs can be grouped based on this 'mechanism of action'.

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In addition to than basal insulin regimens, there are 6 main drugs classes. These include the biguanide metformin, DPP-4 inhibitors, GLP-1 agonists, SGLT2 inhibitors, sulfonylureas (SU) and thiazolidinediones (TZDs). Dual GLP-1/GIP and GLP-1/GCG receptor agonists are also in development. The graphs below can be used to show comparisons of the drugs within each drug class if you wish.

Drug name: The graphs below show the generic drug name, not the brand name. For example, metformin is the generic drug name, whilst the brand name in the USA is Glucophage. We use the generic name, since the brand name may differ in different parts of the world.

Utility: Utility is the name given to a combined outcome, incorporating HbA1c, weight, risk of hypoglycemia, and the dosing regimen (daily tablets, daily injection or weekly injection). The highest utility is achieved with the largest reductions in HbA1c and weight, no increased risk of hypoglycemia, and a daily pill.

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Each drug can be compared on each endpoint separately (e.g. reduction in HbA1c), but it can be very useful to combine results across endpoints to get an overall score. Called a Clinical Utility Index (CUI) or Multi-Criteria Decision Analysis (MCDA), a composite score is determined using weights for each endpoint (more important => higher weighting), and a scale for each endpoint (from worst to best outcomes). Our simple CUI/MCDA example shown below uses the following weights: HbA1c = 60%, Weight = 15%, Hypoglycemia = 15% and Regimen = 10%. Additional endpoints and different weighting/scales can be used, so these results should be seen as illustrative of what can be done.