Abstract:BACKGROUND: Treatment adherence and persistence are crucial to achieve glycemic control in patients with type 2 diabetes (T2D). Early response to a new therapy may lead to improved treatment adherence and associated outcomes.
“…Of the nine included studies, six reported on the association between weight change and adherence, 37–42 two on the relationship between weight change and discontinuation, 43 , 44 and one on weight and both adherence and discontinuation. 45 Presentation of results is reported separately for studies on adherence and for those on discontinuation. Figure 1 Literature review: study selection.…”
Section: Resultsmentioning
confidence: 99%
“…Most were retrospective cohort studies (n = 5) using electronic medical record (EMR) and administrative claims data. 37 , 38 , 40 , 41 , 45 Two studies were prospective and included a 5-year, survey-based study, SHIELD, conducted in a representative US population 39 and a pragmatic, randomized, open-label, parallel group trial (SIMPLE). 42 …”
Section: Resultsmentioning
confidence: 99%
“… 37 , 38 , 40 , 41 , 45 Two studies were prospective and included a 5-year, survey-based study, SHIELD, conducted in a representative US population 39 and a pragmatic, randomized, open-label, parallel group trial (SIMPLE). 42 …”
Section: Resultsmentioning
confidence: 99%
“…Three studies employed objective and widely used claims-based approaches (eg, proportion of days covered [PDC] or medication possession ratio [MPR]). 37 , 38 , 45 Another three studies used subjective measures that rely on patient self-report of adherence (eg, MMAS and the 5-item Medication Adherence Report Scale [MARS-5]). 39–41 In the SIMPLE study, adherence was directly assessed at each clinic encounter by dividing the amount of each drug used by the expected use over the interval between visits.…”
Purpose
Type 2 diabetes (T2D) medication adherence is poor and is impacted by individual drug characteristics. Treatment-associated weight change can affect medication-taking behavior. This review aimed to explore weight change on T2D therapy and consider its impact on adherence and discontinuation.
Methods
Searches were conducted in MEDLINE and EMBASE (2005 to September 2020), and among recent congress abstract books for studies providing data on medication adherence or discontinuation and weight change in people with T2D (PwD).
Results
Nine studies meeting the inclusion criteria were identified from 9188 bibliographic records. All three studies exploring weight change and discontinuation reported weight loss to be associated with higher persistence. Seven studies of varying design explored weight change and adherence. Four reported absolute weight change (kg) and adherence: one pooled data from different diabetes medications and demonstrated that self-reported adherence was significantly associated with weight loss; however, three studies found that weight change in adherent PwD was in the direction of the known weight profile (loss/gain) of the evaluated drug. Categorical weight loss (≥3%) and adherence were reported in two studies: one reported that numerically more adherent versus non-adherent PwD lost ≥3% weight regardless of the drug’s weight profile, the other showed that early weight loss with a glucagon-like peptide-1 agonist was significantly associated with better adherence. One study reported adherence by categorical weight change; as weight loss increased, adherence scores improved, regardless of drug type.
Conclusion
Findings suggest that discontinuation rates may be lower in PwD who lose as compared to those who gain weight on T2D treatment. The evidence base on adherence and weight change is more challenging to interpret due to the range of study designs. Given the importance of weight control in T2D, further research exploring the individual’s treatment, weight journey, and behaviors over time should be undertaken.
“…Of the nine included studies, six reported on the association between weight change and adherence, 37–42 two on the relationship between weight change and discontinuation, 43 , 44 and one on weight and both adherence and discontinuation. 45 Presentation of results is reported separately for studies on adherence and for those on discontinuation. Figure 1 Literature review: study selection.…”
Section: Resultsmentioning
confidence: 99%
“…Most were retrospective cohort studies (n = 5) using electronic medical record (EMR) and administrative claims data. 37 , 38 , 40 , 41 , 45 Two studies were prospective and included a 5-year, survey-based study, SHIELD, conducted in a representative US population 39 and a pragmatic, randomized, open-label, parallel group trial (SIMPLE). 42 …”
Section: Resultsmentioning
confidence: 99%
“… 37 , 38 , 40 , 41 , 45 Two studies were prospective and included a 5-year, survey-based study, SHIELD, conducted in a representative US population 39 and a pragmatic, randomized, open-label, parallel group trial (SIMPLE). 42 …”
Section: Resultsmentioning
confidence: 99%
“…Three studies employed objective and widely used claims-based approaches (eg, proportion of days covered [PDC] or medication possession ratio [MPR]). 37 , 38 , 45 Another three studies used subjective measures that rely on patient self-report of adherence (eg, MMAS and the 5-item Medication Adherence Report Scale [MARS-5]). 39–41 In the SIMPLE study, adherence was directly assessed at each clinic encounter by dividing the amount of each drug used by the expected use over the interval between visits.…”
Purpose
Type 2 diabetes (T2D) medication adherence is poor and is impacted by individual drug characteristics. Treatment-associated weight change can affect medication-taking behavior. This review aimed to explore weight change on T2D therapy and consider its impact on adherence and discontinuation.
Methods
Searches were conducted in MEDLINE and EMBASE (2005 to September 2020), and among recent congress abstract books for studies providing data on medication adherence or discontinuation and weight change in people with T2D (PwD).
Results
Nine studies meeting the inclusion criteria were identified from 9188 bibliographic records. All three studies exploring weight change and discontinuation reported weight loss to be associated with higher persistence. Seven studies of varying design explored weight change and adherence. Four reported absolute weight change (kg) and adherence: one pooled data from different diabetes medications and demonstrated that self-reported adherence was significantly associated with weight loss; however, three studies found that weight change in adherent PwD was in the direction of the known weight profile (loss/gain) of the evaluated drug. Categorical weight loss (≥3%) and adherence were reported in two studies: one reported that numerically more adherent versus non-adherent PwD lost ≥3% weight regardless of the drug’s weight profile, the other showed that early weight loss with a glucagon-like peptide-1 agonist was significantly associated with better adherence. One study reported adherence by categorical weight change; as weight loss increased, adherence scores improved, regardless of drug type.
Conclusion
Findings suggest that discontinuation rates may be lower in PwD who lose as compared to those who gain weight on T2D treatment. The evidence base on adherence and weight change is more challenging to interpret due to the range of study designs. Given the importance of weight control in T2D, further research exploring the individual’s treatment, weight journey, and behaviors over time should be undertaken.
“…This suggests that side effects of GLP-1 RAs are at least in part responsible for lack of persistence to therapy, since administration is similar between once-daily liraglutide and basal insulin, and cost issues are unlikely to underlie medication discontinuation in the context of an RCT. In terms of predicting patterns of adherence and persistence, a recent study by Durden et al [18] found that patients were more likely to adhere to GLP-1 RA therapy over an 18 month period if they experienced an HbA1c reduction of N1% (OR 1.59, 95% CI 1.36, 1.85) or body weight reduction of N3% (OR 1.18, 95% CI 1.02, 1.36) within 3-6 months of drug initiation, compared to those without an early response. These early responders also had significantly lower likelihood of discontinuation compared to patients without early response (HbA1c reduction b1%: OR 0.62, 95% CI 0.53, 0.72; weight reduction b3%: OR 0.81, 95% CI 0.70, 0.94) [18].…”
Section: Glycemic Efficacy Versus Effectivenessmentioning
Managing type 2 diabetes is complex and necessitates careful consideration of patient factors such as engagement in self-care, comorbidities and costs. Since type 2 diabetes is a progressive disease, many patients will require injectable agents, usually insulin. Recent ADA-EASD guidelines recommend glucagon-like peptide 1 receptor agonists (GLP-1 RAs) as first injectable therapy in most cases. The basis for this recommendation is the similar glycemic efficacy of GLP-1 RAs and insulin, but with GLP-1 RAs promoting weight loss instead of weight gain, at lower hypoglycemia risk, and with cardiovascular benefits in patients with pre-existing cardiovascular disease. GLP-1 RAs also reduce burden of glucose self-monitoring. However, tolerability and costs are important considerations, and notably, rates of drug discontinuation are often higher for GLP-1 RAs than basal insulin. To minimize risk of gastrointestinal symptoms patients should be started on lowest doses of GLP-1 RAs and up-titrated slowly. Overall healthcare costs may be lower with GLP-1 RAs compared to insulin. Though patient-level costs may still be prohibitive, GLP-1 RAs can replace 50-80 units of insulin daily and reduce costs associated with glucose self-monitoring. Decisions regarding initiating injectable therapy should be individualized. This review provides a framework to guide decision-making in the real-world setting.
ImportanceAlthough tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available.ObjectiveTo compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting.Design, Setting, and ParticipantsIn this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes through November 3, 2023, were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The analysis was completed on April 3, 2024.ExposuresTirzepatide or semaglutide in formulations labeled for T2D, on or off label.Main Outcomes and MeasuresOn-treatment weight change in a propensity score–matched population, assessed as hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared.ResultsAmong 41 222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 18 386 remained after propensity score matching. The mean (SD) age was 52.0 (12.9) years, 12 970 were female (70.5%), 14 182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5140 patients (55.9%) receiving tirzepatide and 4823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, −2.4%; 95% CI −2.5% to −2.2%), 6 months (difference, −4.3%; 95% CI, −4.7% to −4.0%), and 12 months (difference, −6.9%; 95% CI, −7.9% to −5.8%). Rates of gastrointestinal AEs were similar between groups.Conclusions and RelevanceIn this population of adults with overweight or obesity, use of tirzepatide was associated with significantly greater weight loss than semaglutide. Future study is needed to understand differences in other important outcomes.
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