Switching to Tirzepatide Outweighs Upping Dulaglutide Dose

NEW ORLEANS — For people with type 2 diabetes (T2D) inadequately controlled on submaximal dulaglutide (Trulicity) doses, switching to tirzepatide (Mounjaro) produces significantly greater A1c and weight lowering than does escalating dulaglutide treatment.

“Often, when we are with a patient who is not meeting treatment goals, we need to decide whether to increase a current medication to maximum dose or switch to an alternate medication. With the growing landscape of incretin-based hormone therapies, we now have choice when it comes to prescribing these medications for the treatment of diabetes,” study lead author Liana K. Billings, MD, director of Clinical and Genetics Research in Diabetes and Cardiometabolic Disease and Personalized Medicine at The University of Chicago, Chicago, told Medscape Medical News in an interview.

Billings, vice chair of Research at Endeavor Health (NorthShore Hospitals), Chicago, presented results from Eli Lilly and Company’s multicenter, randomized, open-label, phase 4 SURPASS-SWITCH trial of nearly 3srcsrc patients with T2D on April 4 at the American College of Physicians (ACP-IM) Internal Medicine Meeting 2src25. The findings were simultaneously published in the Annals of Internal Medicine.

“It is clear from the SURPASS-SWITCH study that delaying control by escalating dulaglutide rather than switching to tirzepetide puts [patients] at risk of having blood glucose control above the target range and potentially increases their risk of developing diabetes-related complications,” added Billings.

Asked to comment, Rozalina G. McCoy, MD, associate division chief for Clinical Research, Division of Endocrinology, Diabetes, and Nutrition at the University of Maryland School of Medicine, Baltimore, told Medscape Medical News that while tirzepatide is known to be more potent than earlier-generation glucagon-like peptide 1 (GLP-1) drugs, “Overall, for the questions that they asked, this was very helpful because I think it is important to do within-class comparisons. Otherwise, our treatment decisions are not guided by data.”

But Is Staying Easier Than Switching?

However, McCoy also pointed out that in clinical practice several factors can present barriers to switching treatments. “Health plans vary a lot in terms of which GLP-1 is covered, stepped treatment requirements, and what kind of prior authorizations are required. Sometimes you actually have to fail one drug [at maximal dose] to go to the other. There’s a lot of variability. It’s very difficult, and there’s almost no way to compare formularies.”

Billings said she hadn’t personally come across insurance requirements for reaching maximum doses of incretins before switching, but “fortunately, if this becomes an insurance restriction, we have data from the SURPASS-SWITCH trial, which clearly shows our patients who are not reaching treatment goals will benefit more from switching to tirzepatide rather than continuing to escalate the dulaglutide.”

Does Tirzepatide Bring Too Much Weight Loss?

McCoy also noted that not every patient with T2D needs to lose the large amounts of weight that tirzepatide produces. “For some of our patients, especially those who are taking tirzepatide for diabetes who don’t have severe obesity, you don’t want them to lose all their weight…You get them to [weight] goal, but once you’re at goal, we have no data at all other than if you stop cold turkey, then you’ll regain the weight.”

Moreover, she asked, “If you got to goal with tirzepatide, can we go the other way and go back on dulaglutide so that you basically stay at a stable weight and don’t lose more but hopefully don’t regain weight? This wasn’t studied at all.”

Billings advised monitoring patients at tirzepatide initiation and recommending muscle-strengthening exercises. “If a patient is having rapid weight loss, significant GI [gastrointestinal]-related side effects, not attaining adequate nutrition, I will lower the dose of the incretin-based hormone therapy or discontinue it. If I lower the dose, I monitor carefully for stabilization of weight and improvement in GI side effects.”

Escalate or Switch? Data Point to Latter

In SURPASS-SWITCH, participants included 282 patients with T2D and baseline A1c 7% to <9.5% (mean, 7.82%) on either src.75 mg or 1.5 mg of once-weekly dulaglutide for at least 6 months. They were randomized to either titration of that dose up to 4.5 mg or switched to tirzepatide titrated up to 15 mg (or maximum tolerated doses of both). Most in both groups were also taking oral glucose–lowering agents.

The primary endpoint, A1c change from baseline at week 4src, was a drop of 1.44 percentage points with tirzepatide vs src.67 with dulaglutide, with a significant estimated treatment difference of −src.77 percentage points (P <.srcsrc1). Weight loss at week 4src was also greater with tirzepatide, −1src.5 kg vs −3.6 kg with dulaglutide, again a significant difference (P <.srcsrc1).

The proportions achieving the composite endpoint of A1c 6.5% or less and weight loss of 1src% or greater without hypoglycemia were 47.4% with tirzepatide vs 4.8% with dulaglutide.

Fasting glucose and waist circumference were also reduced to a significantly greater degree with tirzepatide. Both drugs improved lipid profiles, although some of the initial improvement in low-density lipoprotein cholesterol with tirzepatide was lost at 4src weeks. The reason for this is unclear. More information on the cardiovascular effects of tirzepatide will come with the results of the SURPASS-CVOT, due to be completed later in 2src25, Billings and colleagues noted.

Adverse events, including nausea and diarrhea, were similar in the two groups. Hypoglycemia (<54 mg/dL) was more common with tirzepatide (5.8% vs 2.8%), but there were no serious hypoglycemic events in either group.

Billings had received consulting honoraria from Novo Nordisk, Eli Lilly and Company, Endogenex, Sanofi, Dexcom, Bayer, Xeris, Amgen, and Pfizer. McCoy served as a consultant to EmmiEducate (Wolters Kluwer). She is an investigator at the University of Maryland Institute for Health Computing, which is supported by funding from Montgomery County, Maryland, and the University of Maryland Strategic Partnership: MPowering the State, a formal collaboration between the University of Maryland, College Park, and the University of Maryland, Baltimore.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in the Washingto