Alternative dosing regimens of GLP-1 receptor agonists may reduce costs and maintain weight loss efficacy

Abstract

Aims: To discover alternative dosing regimens of incretin mimetics that simultaneously reduce costs and maintain weight loss efficacy. As a secondary objective, we used our results to explore how allocating a limited incretin mimetics budget could affect public health on a national scale.

Materials and methods: We used mathematical modelling and simulation of semaglutide and tirzepatide to investigate dosing regimens which have not yet been studied clinically. For semaglutide, we used a recent pharmacokinetic (PK) and pharmacodynamic (PD) model. For tirzepatide, we used a recent PK model and modelled PD by reparameterizing the semaglutide PD model to fit tirzepatide clinical data.

Results: Reducing dose frequency does not commensurately reduce weight loss. For example, merely switching from one dose per week (q1wk) to one dose every 2 weeks (q2wk) maintains roughly 75% of the weight loss. Furthermore, if the decrease in dose frequency involves an appropriate increase in dose size, then approximately 100% of the weight loss is maintained. In addition, we compared offering incretin mimetics to (1) a fraction of obese US adults with q1wk dosing versus (2) twice as many obese US adults with q2wk dosing. Though scenarios (1) and (2) require the same budget, our analysis suggests that (2) reduces national obesity and mortality to a much greater degree.

Conclusion: Our study highlights the potential utility of alternative dosing regimens of incretin mimetics. Compared with standard once-weekly dosing, costs can be halved and weight loss maintained. These cost-saving results have implications for patients, physicians, insurers, and governments.

Keywords: GIP; GLP‐1; cost‐effectiveness; pharmacodynamics; pharmacokinetics; semaglutide.

FIGURE 1

Reparameterized semaglutide PD model fits tirzepatide weight loss data. Solid curves are the tirzepatide PD model. Markers are clinical trial data from Jastreboff et al. where the error bars around each data point indicate 95% confidence intervals.

FIGURE 2

Alternative dosing regimens of semaglutide decrease costs and maintain efficacy. (A) Steady‐state percent change in body weight as a function of the dosing interval (time between doses). The markers highlight weight loss for once‐weekly dosing (q1wk) versus once every other week dosing (q2wk). (B) How a patient currently on 1.7 mg q1wk can decrease costs and maintain (or improve) efficacy. The markers indicate that switching to q2wk decreases costs by 50% and maintains (i) 69% of their weight loss if the dose size is kept at 1.7 mg and (ii) 82% of their weight loss if the dose size is increased to 2.4 mg. Analogously, panel (C) concerns patients currently on 2.4 mg who decrease their dose frequency.

FIGURE 3

Alternative dosing regimens of tirzepatide decrease costs and maintain efficacy. (A) Steady‐state percent change in body weight as a function of the dosing interval (time between doses). The markers highlight weight loss for once‐weekly dosing (q1wk) versus once every other week dosing (q2wk). (B) How a patient currently on 5 mg q1wk can decrease costs and maintain (or improve) efficacy. The markers indicate that switching to q2wk decreases costs by 50% and maintains (i) 70% of their weight loss if the dose size is kept at 5 mg, (ii) 95% of their weight loss if the dose size is doubled to 10 mg, and (iii) 111% of their weight loss if the dose size is tripled to 15 mg. Analogously, panels (C) and (D) concern patients currently on 10 mg q1wk and 15 mg q1wk, respectively.

FIGURE 4

Exploring public health implications of less frequent dosing at the national scale. Panel (A) estimates how the percentage of obese US adults (BMI ≥30) would decrease if a national supply of semaglutide was administered either (1) to some number of obese US adults at q1wk dosing or (2) to twice as many obese US at q2wk dosing. Panels (B) and (C) are analogous to panel (A) but show the percentage of US adults with class II obesity (BMI ≥35) and class III obesity (BMI ≥40), respectively. Panel (D) then uses the BMI distribution predictions to estimate the number of lives saved. The markers at 3.3 billion mg per year indicate the amount required for a 2.4 mg dose to be taken by either (1) 25% of obese US adults q1wk or (2) 50% of obese US adults q2wk. Similarly, the markers at 6.7 billion mg per year indicate the amount required for a 2.4 mg dose taken by either (1) 50% of obese US adults q1wk or (2) 100% of obese US adults q2wk.