Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates

Abstract

Objectives

The glucagon-like peptide-1 agonist semaglutide and the dual glucose-dependent insulinotropic polypeptide tirzepatide have proven to significantly reduce glucose levels in people with type 2 diabetes. However, the costs needed to achieve a sustained decrease in HbA1c level and disease control with semaglutide and tirzepatide, respectively, are unclear. Therefore, this study aimed to compare the cost of treatment with semaglutide with the cost of treatment with tirzepatide for type 2 diabetes in Austria, the Netherlands, Lithuania, and the United Arab Emirates in order to determine their respective value for money.

Methods

The primary outcome of this analysis was the cost in euros needed to achieve disease control in one person with type 2 diabetes based on the composite endpoint of HbA1c <7%, ≥5% weight loss, and no hypoglycemic events. In addition, analyses regarding the cost needed to reach relevant HbA1c endpoints were performed. Clinical data were obtained from the SURPASS 2 trial, registered at clinicaltrials.gov (NCT03987919), and drug cost was based on wholesale acquisition cost or pharmacy purchase prices from public domains obtained in Q1 of 2023.

Results

The cost needed to achieve disease control in one person with type 2 diabetes (HbA1c <7%, ≥5% weight loss, and no hypoglycemic events) was up to three times lower using semaglutide compared with all three doses of tirzepatide in most markets. In the HbA1c analyses, semaglutide was also found to be the least expensive treatment option.

Conclusion

Semaglutide provides better value for money than tirzepatide for HbA1c-lowering endpoints.

Keywords:

• Diabetes mellitus
• type 2
• treatment cost
• glycemic control
• cost of control

Introduction

About 537 million adults live with diabetes worldwide¹. Of this number, about 90% have type 2 diabetes (T2D), making T2D one of today’s great challenges in public health^2,3. In Europe, 61 million adults live with diabetes, and in the Middle East and North Africa, 73 million people. The International Diabetes Federation estimates that the prevalence of diabetes in adults will increase to 69 million in the European population and 136 million in the Middle East and North Africa by 2045¹.

It is well known that several comorbidities are associated with T2D, including renal, cardiovascular, neurological, and retinal complications, especially if glycemic targets are not met^4–9. A newly published systematic review of existing international evidence-based guidelines on T2D management recommended target HbA1c levels below 7% depending on individual patient characteristics¹⁰. The 2022 consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) established a series of new recommendations for the management of T2D. These include a greater focus on the holistic approach to diabetes management, including more emphasis on weight management as part of the solution to hyperglycemia¹¹.

Glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor co-agonists like tirzepatide are effective treatment options for people with T2D due to their HbA1c-lowering effects that lead to glucose control¹². Semaglutide and tirzepatide are currently two of the most modern incretin mimetic drugs, and clinicians or healthcare providers are in a position where one of these products will likely be the optimal treatment choice from the medical perspective. However, as the prevalence of T2D increases, rising drug costs might become a significant burden on healthcare systems, and it becomes more and more relevant to consider the cost-effectiveness of HbA1c-lowering treatments in order to bring health economic prioritizations in line with the medical evidence.

Clinical trial data from the SURPASS 2 trial comparing semaglutide and tirzepatide showed that treatment with tirzepatide was superior to semaglutide with respect to achieving endpoints related to HbA1c levels¹². However, when assessing the cost-effectiveness of HbA1c-lowering treatments, it is important to consider the needed doses and cost of reaching controlled levels of HbA1c.

Therefore, the objective of this paper was to estimate the cost of control (CoC) of T2D to understand and compare the cost relative to the treatment effect with semaglutide versus tirzepatide.

Methods

This CoC study is covering treatment outcomes related to control of HbA1c levels in people with T2D. A CoC analysis is a way of examining the cost needed to achieve disease control, defined by clinically relevant health outcomes, in one patient. In this paper, the CoC in T2D was compared for treatment with semaglutide versus tirzepatide in the Netherlands, Austria, Lithuania, and the United Arab Emirates (UAE).

The comparison analyses include semaglutide 1 mg once weekly and tirzepatide at three different doses (5 mg, 10 mg, and 15 mg) once weekly. As this study focuses on the cost of reaching HbA1c control in people with diabetes the included treatments and doses are those labeled for diabetes. Therefore, different doses of, i.e. semaglutide, including the 2.4 mg, will not be considered in this paper as the 2.4 mg dose is used in obesity. Drug prices in the Netherlands were obtained in pharmacy purchase prices (PPP) from “Farmacotherapeutisch Kompas”¹³; prices in Austria were obtained in wholesale purchasing prices (WPP) from “Warenverzeichnis”¹⁴; prices in the UAE were obtained in PPP from the department of health¹⁵; and prices in Lithuania were obtained in WPP from the national drug control agency¹⁶. Prices in the UAE were obtained in Emirati dirham (AED) and converted to euros (EUR) using the average 2023 exchange rate of AED 100 = EUR 24.91.

Data source for treatment efficacy

Efficacy data were extracted from the published results of the SURPASS 2 trial, which have been registered at clinicaltrials.gov (NCT03987919). The SURPASS 2 trial compared the efficacy of once weekly semaglutide 1 mg with that of tirzepatide 5 mg, 10 mg, and 15 mg in participants with T2D. SURPASS 2 reported the mean HbA1c change; the number needed to treat (NNT) for one participant to achieve HbA1c control, defined by HbA1c level <7%; and NNT for one participant to reach a composite control, defined by HbA1c <7%, ≥5% weight loss, and no hypoglycemia^12,17. In the SURPASS 2 trial, 1,879 people with diabetes received at least one dose of tirzepatide or semaglutide. Of that group, 470, 469, and 470 were treated with tirzepatide 5 mg, 10 mg, and 15 mg, respectively, and 469 were treated with semaglutide. The demographics and clinical baseline characteristics were similar across the treatment groups. In the three tirzepatide groups, mean age ranged from 55.9 to 57.2; in the semaglutide group, mean age was 56.9. Baseline mean glycated hemoglobin levels were 8.32, 8.3, and 8.26 in the three tirzepatide groups (5 mg, 10 mg, and 15 mg), and 8.25 in the semaglutide group. Mean duration of T2D ranged from 8.4 to 9.1 years in the tirzepatide groups, and it was 8.3 in the semaglutide group. Overall mean duration of T2D was 8.6 years. All analyses were based on the assumption of a linear treatment effect during the treatment period.

Primary outcome measures

The primary outcome in this study was the cost needed to achieve disease control in one person with T2D based on the composite endpoint HbA1c <7%, ≥5% weight loss, and no hypoglycemia. The primary outcome has been chosen for this analysis as it is in line with the current holistic treatment approach in T2D care and management of hyperglycemia. According to the latest (2022) consensus report by ADA and EASD a weight loss of 5–15% should be a primary target for many people living with T2D and though a higher magnitude of weight loss confers better outcomes for most people, a target of 5% is reasonable and can be expected to have clinical benefits¹¹. Thus, the applied endpoint acknowledges that appropriate HbA1c targets should be considered in light of the risk of hypoglycemic events and the fact that a sustained weight loss of ≥5% is a means of improving glycemic control^11,18,19.

The cost needed to achieve disease control (composite endpoint) in one person with T2D was calculated as 1, divided by the share of participants from the SURPASS 2 trial who achieved HbA1c <7%, ≥5% weight loss, and no hypoglycemia multiplied by the country-specific yearly drug cost.

Secondary outcome measures

The secondary outcomes of this study were

• The CoC for one person with T2D, at HbA1c level of <7%, using either semaglutide or tirzepatide; and

• The cost needed for a 1 percentage point reduction in HbA1c level.

The cost needed for a 1 percentage point reduction in HbA1c level was calculated by multiplying the country-specific weekly drug cost by the 40 weeks of follow-up from the SURPASS 2 trial and dividing it by the mean percentage point change in HbA1c level for each treatment arm.

Results

Primary outcomes

In the SURPASS 2 trial, 51% of participants treated with once weekly semaglutide 1 mg achieved the triple composite endpoints of HbA1c <7%, ≥5% weight loss, and no hypoglycemia. For tirzepatide, 62%, 76%, and 81% of participants treated with once weekly tirzepatide 5 mg, 10 mg, and 15 mg, respectively, achieved this endpoint. Thus, to reach one person with T2D in composite control, 1.96 persons need to be treated with semaglutide 1 mg, 1.61 persons need to be treated with tirzepatide 5 mg, 1.32 persons need to be treated with tirzepatide 10 mg, and 1.23 participants need to be treated with tirzepatide 15 mg. Table 1 presents the relevant clinical outcomes from the SURPASS 2 trial and the estimated CoC.

Table 1. Cost of control at HbA1c <7%, ≥5% weight loss, and without hypoglycemia.

	Weekly doses	Annual drug cost (EUR)	Achieved composite endpoint of HbA1c <7%, ≥5% weight loss, and without hypoglycemia	NNT to achieve one composite control	Cost of reaching one composite control (EUR)	Relative difference in cost of reaching control
The Netherlands	Semaglutide 1 mg	1,138	51%	1.96	2,230	–
	Tirzepatide 5 mg	4,869	62%	1.61	7,852	3.52
	Tirzepatide 10 mg	4,869	76%	1.32	6,406	2.87
	Tirzepatide 15 mg	4,869	81%	1.23	6,010	2.69
Austria	Semaglutide 1 mg	1,017	51%	1.96	1,993	–
	Tirzepatide 5 mg	4,550	62%	1.61	7,339	3.68
	Tirzepatide 10 mg	4,550	76%	1.32	5,987	3.00
	Tirzepatide 15 mg	4,550	81%	1.23	5,617	2.82
Lithuania	Semaglutide 1 mg	1,245	51%	1.96	2,442	–
	Tirzepatide 5 mg	5,096	62%	1.61	8,219	3.37
	Tirzepatide 10 mg	5,096	76%	1.32	6,705	2.75
	Tirzepatide 15 mg	5,096	81%	1.23	6,291	2.58
The UAE	Semaglutide 1 mg	3,161	51%	1.96	6,197	–
	Tirzepatide 5 mg	4,782	62%	1.61	7,712	1.24
	Tirzepatide 10 mg	4,782	76%	1.32	6,292	1.02
	Tirzepatide 15 mg	4,782	81%	1.23	5,903	0.95

In the Netherlands, the cost of achieving one person with T2D in control was EUR 2,230 for semaglutide-treated persons and EUR 7,852, EUR 6,406 and EUR 6,010 for persons treated with tirzepatide 5 mg, 10 mg, and 15 mg, respectively. Thus, the CoC was about 3-times higher when using tirzepatide at any dose compared with semaglutide. In Austria and Lithuania, the CoC with tirzepatide ranged from approximately double the cost to about 3.5-times the cost compared with treatment with semaglutide. In the UAE, the CoC of tirzepatide was similar to that of semaglutide but slightly higher at the 5 mg dose (Figure 1).

Figure 1. Cost of control at HbA1c <7%, ≥5% weight loss, and without hypoglycemia (EUR).

Secondary outcomes

In the SURPASS 2 trial, 79% of participants treated with once weekly semaglutide 1 mg, 82% of participants treated with once weekly tirzepatide 5 mg, and 86% of participants treated with once weekly tirzepatide 10 mg or 15 mg achieved an HbA1c level of <7%¹². This means that to reach one person with T2D at HbA1c <7%, 1.27 persons need to be treated with semaglutide 1 mg, 1.22 persons need to be treated with tirzepatide 5 mg, and 1.16 persons need to be treated with tirzepatide 10 mg or 15 mg. Table 2 presents the relevant clinical outcomes from the SURPASS 2 trial and the estimated CoC.

Table 2. Cost of control at HbA1c <7%.

	Weekly doses	Achieved HbA1c <7%	NNT to reach one HbA1c control (<7%)	Cost of reaching one HbA1c control (EUR)	Relative difference in cost of reaching HbA1c control
The Netherlands	Semaglutide 1 mg	79%	1.27	1,440	–
	Tirzepatide 5 mg	82%	1.22	5,937	4.12
	Tirzepatide 10 mg	86%	1.16	5,661	3.93
	Tirzepatide 15 mg	86%	1.16	5,661	3.93
Austria	Semaglutide 1 mg	79%	1.27	1,287	–
	Tirzepatide 5 mg	82%	1.22	5,549	4.31
	Tirzepatide 10 mg	86%	1.16	5,291	4.11
	Tirzepatide 15 mg	86%	1.16	5,291	4.11
Lithuania	Semaglutide 1 mg	79%	1.27	1,576	–
	Tirzepatide 5 mg	82%	1.22	6,215	3.94
	Tirzepatide 10 mg	86%	1.16	5,926	3.76
	Tirzepatide 15 mg	86%	1.16	5,926	3.76
The UAE	Semaglutide 1 mg	79%	1.27	4,001	–
	Tirzepatide 5 mg	82%	1.22	5,831	1.46
	Tirzepatide 10 mg	86%	1.16	5,560	1.39
	Tirzepatide 15 mg	86%	1.16	5,560	1.39

In the Netherlands, the cost of achieving one person with T2D at an HbA1c level of <7% was EUR 1,440 for semaglutide 1 mg, EUR 5,937 for treatment with tirzepatide 5 mg and EUR 5,661 for treatment with tirzepatide 10 mg or 15 mg. Thus, the CoC was about 4-times higher when using tirzepatide at any dose compared with semaglutide. In Austria and Lithuania, the CoC at an HbA1c level of <7% was 3–4+-times higher using tirzepatide compared with semaglutide, and in the UAE, the CoC was about 40% higher using tirzepatide compared with semaglutide (Figure 2).

Figure 2. Cost of control at HbA1c <7% (EUR).

In the SURPASS 2 trial, participants treated with semaglutide 1 mg/week achieved an average decrease in HbA1c levels of 1.86 percentage points. For participants treated with tirzepatide 5 mg/week, 10 mg/week, and 15 mg/week, the average decrease was 2.01, 2.2, and 2.3 percentage points, respectively. The cost of 40 weeks of treatment with semaglutide 1 mg/week ranged from EUR 782 to EUR 2,257 in the four countries. The cost of treatment with tirzepatide at all doses ranged from EUR 3,500 to EUR 3,920. Relevant clinical outcomes from the SURPASS 2 trial and the estimated treatment cost of a 1 percentage point decrease in HbA1c level are presented in Supplementary Table S1.

In the Netherlands, the cost needed to achieve a 1 percentage point reduction in HbA1c level was EUR 470 with semaglutide 1 mg/week and EUR 1,863, EUR 1,672, and EUR 1,628 with tirzepatide 5 mg/week, 10 mg/week, and 15 mg/week, respectively. Thus, the cost needed for a 1 percentage point reduction in HbA1c level was between EUR 1,158 and EUR 1,393 higher with tirzepatide at any dose compared with semaglutide 1 mg/week. In Austria, Lithuania, and the UAE, respectively, the cost needed for a 1 percentage point reduction in HbA1c level was from EUR 1,101 to EUR 1,321; EUR 1,189 to EUR 1,435; and EUR 292 to EUR 523 lower when using semaglutide compared with tirzepatide. The cost needed to achieve a 1 percentage point reduction is shown in Figure 3.

Figure 3. Cost needed to achieve a 1 percentage point HbA1c decrease (EUR).

Discussion

The treatment cost of semaglutide was generally lower than the treatment cost of tirzepatide for included clinical outcomes. The present study showed that the CoC, defined by HbA1c <7%, ≥5% weight loss, and no hypoglycemic events, was considerably lower with semaglutide compared with tirzepatide in the Netherlands, Austria, and Lithuania. In the UAE, the CoC was similar using semaglutide and tirzepatide. Additionally, when analyzing the cost incurred to reach clinical HbA1c targets, the study found that semaglutide was better value for money compared with tirzepatide at any dose.

Lowering HbA1c levels to meet glycemic targets is of immense importance in T2D care. Attaining recommended glycemic targets significantly reduces the onset of comorbidities as well as the progression of comorbidities, particularly in microvascular complications¹¹. Therefore, cost-effective pharmacologic treatment options to manage HbA1c levels in combination with behavioral weight management interventions are required in the care of T2D¹¹. Clinical guidelines from ADA and EASD recommend an HbA1c target of <7% for most people with T2D, which for the majority of people with T2D has been found to be a safe HbA1c level that also provides microvascular benefits¹¹.

Generally, the risk of hypoglycemia associated with GLP-1 receptor agonists is low because the treatment option mainly lowers glucose levels by stimulating secretion of glucose-dependent insulin²⁰. In the SUSTAIN 6 study, similar rates of hypoglycemia were identified among participants treated with semaglutide and placebo²¹. Moreover, the SURPASS 2 trial identified different risk profiles related to hypoglycemia in favor of semaglutide compared with tirzepatide 5 mg and 15 mg¹².

The safety of GLP-1 receptor agonists has been well established and, to date, no major safety concerns have been associated with semaglutide treatment. Compared with placebo and active comparators, semaglutide has been found to have an overall beneficial risk/benefit profile for treatment of T2D^12,20. Additionally, semaglutide has been found to significantly reduce the risk of major adverse cardiovascular events (MACE) in adults with T2D and known cardiovascular disease^21,22. Recommendations R from ADA and EASD list GLP-1 receptor agonists or sodium–glucose cotransporter-2 inhibitors as the preferred treatment option in people with T2D and known cardiovascular disease¹¹. Data on cardiovascular benefits do not exist for tirzepatide. When considering the cost associated with treatment of serious adverse events and MACE, the cost savings from using semaglutide instead of tirzepatide in the care for people with T2D are likely even higher than estimated in this study, where only the direct treatment cost was included in cost estimates.

This CoC analysis had some strengths and limitations. The methodology used in this analysis is a simple and transparent way to estimate the CoC defined by clinically relevant outcomes. The cost needed for a 1 percentage point decrease in HbA1c was calculated as the total cost divided by the clinical outcomes, which assumes a linear correlation. Cost inputs in the analysis were obtained from publicly available sources. However, the actual drug prices used in the respective countries can deviate from the prices available to the public. The clinical results used for this study were obtained from the SURPASS 2 trial, a phase 3 study. The current study presented CoC for countries that were not included in SURPASS 2, which constitutes a possible limitation due to restricted generalizability, although this risk is minimized by the global reach of phase 3 programs. This CoC analysis estimated the treatment cost of achieving relevant glycemic outcomes and did not consider cost of complications or quality-of-life, and, as such, should be used as a preliminary comparative measure. Nevertheless, similar analyses have previously been found to correlate with published cost-effectiveness analysis results²³.

Conclusion

The results from this study support the economic advantage of using semaglutide in comparison with tirzepatide. In the four included countries, semaglutide was found to be the least expensive treatment option for managing hyperglycemia in T2D, except for the UAE, where semaglutide was the second-least expensive. In conclusion, semaglutide provides better value for money in the management of people with T2D compared with tirzepatide.

Transparency

Author contributions

Mette Bøgelund, Amaury Basse, Olga Barszczewska and Hongye Ren were involved in conceptualizing and designing the study. Signe Baattrup Reitzel analyzed and interpreted the data and drafted the paper. All authors critically revised the paper and gave final approval for the version to be published. All authors agree to be accountable for the work presented in this paper.

Ethics statements

Results from the SURPASS 2 trial (NCT03987919) were applied in this study.

Acknowledgements

No assistance in the preparation of this article is to be declared.

Declaration of funding

The analysis presented in this article and manuscript writing was supported by Novo Nordisk North West Europe. Novo Nordisk reviewed and provided feedback on the manuscript.

Declaration of financial/other relationships

Hongye Ren, Olga Barszczewska, and Amaury Basse are employees of Novo Nordisk A/S. Signe Baattrup Reitzel and Mette Bøgelund are employees of EY Denmark, which is a paid vendor of Novo Nordisk A/S. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary materials.