Talk This Way: Kicking Off the T2D-Obesity Conversation For Optimal Treatment

"Sometimes when it looks like I’m deep in thought I’m just trying not to have a conversation with people." — Pete Wentz, bassist and lyricist for the rock band Fallout Boy.

For clinicians, being "deep in thought" during a patient encounter may mean being focused on their device, scrolling through the various pharmaceutical-based therapies, checking professional guidelines, and finally settling on the optimal treatment course for their patients with obesity.

But it’s not enough to hand someone an instrument and push them on stage — there has to be give and take between the performers (clinicians) and their audience (patients) when the goal is selecting the optimal dual-effect antiobesity and antidiabetic medications for T2D management.

Strategies on kicking off those conversations to establish goals and treatment plans in obesity need to be based on the impact of the encore as much as the opening song. "If a communicator only considers the immediate impact of their words, they are likely to conclude that honesty and benevolence are fundamentally at odds," explained Emma E. Levine, PhD, of the University of Chicago, and co-authors in a 2020 Current Opinion in Psychology article. "However, if a communicator considers the long-term consequences of their words, they are more likely to recognize that honesty and benevolence are actually compatible."

Short-Term: T2D On Track

If a patient has obesity and T2D, clinicians and patients will no doubt be in harmony that the T2D needs to be addressed first, especially since it is difficult to miss the news coverage showing that semaglutide, tirzepatide, and other agents have demonstrated efficacy in T2D and weight loss, although not without some controversy.

One way to get patients fired up about T2D treatment, and its potential benefits for achieving healthy weight, is by sharing trial data. For instance, back in 2017, the 1-mg injection of semaglutide gained FDA approval after many SUSTAIN studies turned in impressive results, either on its own or as an add-on therapy (SUSTAIN OPTIMIZE is ongoing). Then 2.4-mg once weekly injection of semaglutide nabbed FDA approval in 2021 thanks to positive data from multiple STEP trials. Across the trials, that dose of semaglutide was tied to mean weight losses of 14.9%‐17.4% in people with overweight/obesity, but without T2D, from baseline to week 68.

A 2023 phase II trial of once weekly cagrilintide/semaglutide (both escalated to 2.4 mg) demonstrated the combination’s efficacy as a way for patients with T2D and obesity to improve glycemic control (mean change in hemoglobin A1c [HbA1c] from baseline to week 32 of 2.2 percentage points vs <2 percentage points with other agents) and shed pounds (mean change in body weight from baseline to week 32 of -15.6% vs <10% with others agents).

Tirzepatide was initially approved in 2022 as an add-on to diet and exercise to improve glycemic control in patients with T2D, and it was later approved in 2023 as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI ≥30 kg/m², or ≥27 kg/m² in the presence of at least one weight-related comorbid condition, such as T2D, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.

One of the trials that backed tirzepatide’s FDA approval, the phase III SURMOUNT-2 trial, showed that the agent led to a mean weight loss of 12.8% and 14.7%, respectively, at doses of 10 and 15 mg in adults with T2D and a BMI ≥27 kg/m². More participants met body-weight reduction thresholds of ≥5%. Most frequent adverse events (AEs) were mild-to-moderate gastrointestinal (GI) events.

Data from multiple SURPASS trials put the spotlight on the higher level of benefit with GLP-1 RA/GIP agonists for slashing HbA1c by at least 2%. As for weight loss, reductions went as high as 8 kg (about 17 lbs), and the agent often turned in better results for shedding pounds than semaglutide, insulin glargine, and other T2D medications. Ongoing SURPASS studies, such as SURPASS-EARLY and SURPASS-SWITCH will test tirzepatide against other antihyperglycemic medications.

In a 2019 Applied Clinical Trials survey-based study on recruiting patients for trials, Lindsey Wahlstrom-Edwards, MPH, CPH, of Antidote Technologies in North Miami Beach, Florida, and Anne-Marie Hess, of SCORR Marketing in Kearny, Nebraska, found that respondents stressed the importance of "[having] someone available to answer questions throughout the study (66%) and their doctor’s support for their decision to participate (50%)."

Long-Term: Obesity Opener

Clinicians have reported other reasons why they avoided working with a patient on weight management. In a 2022 SSM-Qualitative Research in Health study, Madeleine Tremblett, PhD, MSc, of the University of Oxford in England, and co-authors, explained that other factors primary care physicians (PCP) cited were fear of offending their patient; a belief that weight management interventions are ineffective; and, the ubiquitous, lack of time.

But Temblett’s group also noted that patients have said they want weight management to be a part of their PCP experience. "Patient reflections suggest they may be more welcomed when weight loss was specifically related to have a positive impact on current health condition," they wrote.

Based on their study on "opportunistic weight loss advice" done with PCPs and patients, they pointed out that "[g]eneric recommendations tended to prompt passive resistance to the advice. A lack of delicacy features in the [PCP’s] talk also tended to prompt passive resistance to the advice." Delicacy features include "softening the advice," so instead of telling patients they must hit a hard-and-fast guideline-directed weight loss goal, recommend that they begin with a goal of losing "a little bit of weight" so that the task doesn’t seem insurmountable.

This approach also gives clinicians the opportunity to sing the praises of a "weight-centric approach to T2D when obesity is also present," noted SURMOUNT-2 investigator W. Timothy Garvey, MD, University of Alabama at Birmingham in a 2023 American Diabetes Association press release. "We are encouraged by these weight loss and glycemic control results [in SURMOUNT-2], especially as weight loss interventions are typically less effective in patients in diabetes."

SURPASS data can also drive home the message to patients that dual-effect medication will be a two-for-one deal: In a 2023 Cureus review, Suganya Giri Ravindran, MD, of the California Institute of Behavioral Neurosciences & Psychology in Fairfield, and co-authors summarized that "for body weight…tirzepatide considerably outperformed dulaglutide, semaglutide, degludec, and glargine in causing weight loss. The likelihood that patients using tirzepatide would achieve an Hba1C of 5.7% was higher…the waist circumference also decreased by 4.43 cm when using tirzepatide compared to semaglutide or dulaglutide and by roughly 4.83 cm when compared with a placebo."

Finally, clinicians should also be willing to meet patients half way. In a 2024 New England Journal of Medicine perspective, Illya Golovaty, MD, and Scott Hagan, MD, both of the University of Seattle, noted that "[m]ost adults who want to lose weight don’t participate in lifestyle-intervention programs, in part because of the substantial time commitment involved and a shortage of affordable programs."

The SURMOUNT-2 and SURPASS trials are supported by Eli Lilly.

Levine and co-authors reported no relationships relevant to the contents of this paper to disclose.

The study by Tremblett’s group was supported by the British Heart Foundation, the UK National Prevention Research Initiative, Alzheimer’s, Biotechnology and Biological Sciences Research Council, Cancer Research UK, Scottish Government Health Directorate, Department of Health, Diabetes UK, Economic and Social Research Council, Engineering and Physical Sciences Research Council, Health and Social Care Research Division, Public Health Agency Northern Ireland, MRC, Stroke Association, Wellcome Trust, Welsh Government, and the World Cancer Research Fund. Tremblett reported no relationships relevant to the contents of this paper to disclose. Co-authors reported support from Novo Nordisk, the National Institute for Health Research (NIHR), the NIHR Oxford and Thames Valley Applied Research Collaboration, the NIHR Oxford Biomedical Research Centre, the Mildred Blaxter postdoctoral fellowship/Foundation for the Sociology of Health and Illness, and NIHR Primary Care Research.

Golovaty and Hagan reported employed with the Department of Veterans Affairs.

Levine EE, et al "Difficult conversations: navigating the tension between honesty and benevolence" Curr Open Psychol 2020;31:38-43. DOI: 10.1016/j.copsyc.2019.07.034.

Tremblett M, et al "Talking delicately: Providing opportunistic weight loss advice to people living with obesity" SSM Qual Res Health 2022. DOI: 10.1016/j.ssmqr.2022.100162.

Golovaty I, Hagan S "Direct-to-consumer platforms for new antiobesity medications — Concerns and potential opportunities" N Engl J Med 2024;390:677-680. DOI: 10.1056/NEJMp2312816.