- Patients with poorly controlled type 2 diabetes despite being on dulaglutide had better outcomes if they switched to tirzepatide than if they upped their dulaglutide dose.
- In this randomized trial, the group switching to tirzepatide had a greater reduction in HbA1c at week 40 (1.44% vs 0.67%).
- The group assigned to tirzepatide also had a greater reduction in average weight (23.1 vs 7.9 lb).
Diabetes patients on dulaglutide (Trulicity) had better glycemic control and more weight loss if they switched to tirzepatide (Mounjaro) rather than increasing the dose of the earlier-generation GLP-1 receptor agonist, an open-label randomized trial found.
Among 282 adults with inadequately controlled type 2 diabetes despite treatment with dulaglutide, those who switched to tirzepatide had a 1.44% reduction in HbA1c at week 40 compared with a 0.67% reduction for those who escalated their dulaglutide dose to 4.5 mg (P<0.001).
Switching to tirzepatide also led to a weight loss of 10.5 kg (23.1 lb) compared with 3.6 kg (7.9 lb) with the higher dulaglutide dose (P<0.001), according to Liana Billings, MD, of the University of Chicago, and colleagues in Annals of Internal Medicine.
"Results from SURPASS-SWITCH suggest that escalating dulaglutide is not as effective in reducing HbA1c and may further delay diabetes control than switching to tirzepatide," they wrote. "Further research is needed to assess the potential benefit of early glycemic control via early medication switching on longer-term clinical outcomes."
The study findings were also presented at the American College of Physician's Internal Medicine Meeting 2025 in New Orleans.
The SURPASS clinical program supported tirzepatide's initial approval for type 2 diabetes. Later, it picked up indications for chronic weight management and obstructive sleep apnea.
When healthcare providers are deciding between escalating the dose of existing medications and switching antihyperglycemic agents, there are various factors to consider, the researchers advised.
"As people age and their risk for complications and comorbidities increases, it may be necessary to initiate or consider switching to an antihyperglycemic medication that has an efficacy and safety profile that better addresses evolving health needs," they said. "An important consideration is lowering the risk for incident or secondary cardiovascular events given that cardiovascular disease is a major cause of death in patients with diabetes."
"Other clinical considerations when switching medications include possible adverse reactions and tolerability and the extra care and costs, dosing and escalation schedules, and trials showing benefit for other cardiorenal or weight considerations," they suggested.
For the current study, 139 patients were randomly assigned to tirzepatide 15 mg or a maximum tolerated dose and 143 to dulaglutide 4.5 mg or a maximum tolerated dose. At baseline, average diabetes duration was 11.2 years, HbA1c was 7.82%, and body weight was 96.9 kg (213.6 lb). Baseline dulaglutide dose was 1.5 mg once weekly in two-thirds of participants. A total of 89.5% of participants were able to achieve the maximum dose of dulaglutide by the end of the trial compared with 79.9% of those on tirzepatide.
Participants who increased the dulaglutide dose reduced their HbA1c to 7.15%, while those switching to tirzepatide reduced theirs to 6.38% by week 40.
Average weight dropped from 98.1 kg (216.3 lb) to 86.7 kg (191.1 lb) in the tirzepatide arm as compared with 96 kg (211.6 lb) to 93.5 kg (206.1 lb) in the dulaglutide dose-escalation arm.
Billings and co-authors said that weight loss plateaued around week 8 with dulaglutide, but tirzepatide users still hadn't reached a nadir by the end of the trial.
"The lack of plateau weeks after achieving a stable dose in the tirzepatide group is consistent with the observed weight loss over time from baseline to primary endpoint in other SURPASS phase III studies," they said.
Both the tirzepatide and dulaglutide groups had reductions in serum cholesterol, LDL, very-low-density lipoprotein, and triglycerides, and increased high-density lipoprotein.
Compared with dulaglutide, the tirzepatide group had a greater reduction in fasting serum glucose by week 40 (estimated treatment difference -18.4 mg/dL, 95% CI -25.5 to -11.2).
Tirzepatide switchers also had a 5.1 cm greater reduction in waist circumference than those who increased their dulaglutide dose.
Adverse event rates were similar between the two groups, with four patients on tirzepatide and one patient on dulaglutide discontinuing due to adverse events. As expected, the most common treatment-emergent adverse events were nausea and diarrhea. There were more hypoglycemic events in the tirzepatide group.
One death occurred in each group, both of which were not considered to be related to the study treatment.
Because the study only looked at patients who switched from dulaglutide, the findings shouldn't be generalized to other GLP-1 receptor agonists, the researchers noted. They also didn't assess the superiority of switching to tirzepatide versus switching to other highly effective alternative antihyperglycemic agents.
Disclosures
The study was funded by Eli Lilly and Company.
Billings reported relationships with Eli Lilly and Company, Bayer, Dexcom, Endogenex, Novo Nordisk, Pfizer, Sanofi, and Xeris Pharmaceutical.
Other co-authors also reported relationships with Eli Lilly and Company.
Primary Source
Annals of Internal Medicine
Source Reference: Billings LK, et al "Comparison of dose escalation versus switching to tirzepatide among people with type 2 diabetes inadequately controlled on lower doses of dulaglutide: a randomized clinical trial" Ann Intern Med 2025; DOI: 10.7326/ANNALS-24-03849.
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