Long-Term Benefits of Composite Treatment Targets in Type 2 Diabetes Management

Sustained Composite Treatment Targets Enhance Clinical and Economic Outcomes in Type 2 Diabetes

A recent modeling study examines the long-term benefits of achieving composite treatment targets—defined as stringent glycemic control (HbA1c ≤6.5%), weight reduction (≥10%), and absence of hypoglycemia—in predominantly Chinese patients with type 2 diabetes (T2D) inadequately controlled on metformin and/or sulfonylurea. Drawing from the SURPASS-AP-Combo trial, the analysis projects 30-year outcomes using the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS OM2), revealing that sustained achievement of these composite treatment targets yields incremental quality-adjusted life years (QALYs) of 0.31 to 0.56 and cost savings of ¥22,336 to ¥53,234 per patient, depending on the duration of sustainment (3, 5, or 10 years). These gains stem from reduced macro- and microvascular complications, fewer hypoglycemia events, and delayed treatment intensification to basal-bolus insulin, underscoring the value of holistic T2D management aligned with international and Chinese guidelines.

Dose-Response: Longer CTT Sustainment Boosts Benefits

The study’s core finding on the dose-response relationship between composite treatment targets sustainment duration and patient outcomes, highlighted that longer periods amplifying both clinical and economic benefits. For instance, patients achieving CTT for 10 years in the base-case scenario (CTT 1: HbA1c ≤6.5%, ≥10% weight loss, no hypoglycemia) experienced 0.56 QALYs gained and ¥53,234 in savings compared to those failing CTT, driven by a 6.6% lower cumulative incidence of complications at 30 years, including reductions in congestive heart failure (from 4.4% to 3.8%), myocardial infarction (from 11.7% to 10.1%), stroke (from 18.0% to 17.2%), and amputation (from 7.9% to 5.9%). These improvements were supported by trial data showing Achieved group reductions in HbA1c by 1.81% and weight by 8.81 kg versus minimal changes in the Failed group. Shorter sustainments (3 or 5 years) yielded proportionally smaller gains (0.31 QALYs and ¥22,336 savings for 3 years; 0.40 QALYs and ¥32,692 for 5 years), emphasizing the cumulative impact of early, sustained control. Scenario analyses with less stringent CTT (e.g., HbA1c <7% and ≥5% weight loss) confirmed persistent but attenuated benefits, with 0.55 QALYs and ¥52,869 savings for 10 years under CTT 2, reinforcing the model’s robustness across guideline variations from the American Diabetes Association (ADA), American Association of Clinical Endocrinology (AACE), and Chinese Diabetes Society (CDS).

China-Tailored UKPDS OM2 Simulations

The model, using the UKPDS OM2, was a probabilistic discrete-time illness-death model that simulates T2D progression by integrating 13 risk factors (e.g., HbA1c, body mass index [BMI], systolic blood pressure) derived from 5,102 UKPDS patients, with adaptations here for Chinese-specific inputs to project complications, mortality, QALYs, and costs over 30 years. Baseline demographics from SURPASS-AP-Combo (n=83.4% Chinese; mean age 54.1 years, HbA1c 8.71%, BMI 27.88 kg/m²) informed patient profiles, generated via Monte Carlo simulations (10,000 iterations) with a 5% annual discount rate for costs and effects. Efficacy data categorized patients into Achieved or Failed groups based on end-of-trial CTT status, with sustained benefits assumed for 3–10 years before reverting to natural UKPDS trajectories; treatment intensification to basal-bolus insulin occurred at HbA1c thresholds (e.g., >8.0% for CTT 1), incorporating literature-derived effects like 1.5% HbA1c reduction but increased hypoglycemia risk. Utility values reflected baseline T2D (0.85) decremented for complications (e.g., -0.06 for myocardial infarction) and overweight (-0.02), sourced from Chinese studies, while costs (e.g., ¥2,093 annually without complications, quadrupling with multiple events; ¥1,378 per hypoglycemia hospitalization) were drawn from national claims and procurement data. This adaptation enhances applicability to China’s T2D burden—116 million cases in 2021, with 50% failing HbA1c <7%—by addressing gaps in prior evidence on holistic targets.

Value-Based Pathways for T2D Innovations

The demonstrated QALY gains and cost offsets from CTT achievement position holistic therapies—such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or glucose-dependent insulinotropic polypeptide/GLP-1 RA combinations like tirzepatide, tested in SURPASS-AP-Combo—as high-value interventions for payers, potentially justifying premium pricing through reduced long-term expenditures on complications (e.g., ¥67.52 million annually nationwide for hypoglycemia). In HEOR terms, these results align with trends toward composite endpoints in outcomes research, supporting guideline shifts toward individualized targets that balance efficacy, safety, and weight management, as seen in ADA/CDS recommendations for HbA1c <7% with ≥5% weight loss.

From a market access perspective, the model’s conservative estimates (underestimating weight’s broader effects and novel agents’ cardiorenal benefits) suggest opportunities for value-based reimbursement in China, where T2D drives 11.5 million disability-adjusted life years; integrating CTT into health technology assessments could expedite approvals for agents delaying intensification by 9 years, as observed here. Similar modeling in Italian and UK settings reported 0.23–0.5 QALY gains from intensive control, implying global scalability—yet China’s volume-based procurement (e.g., insulin pricing) must evolve to incentivize low-hypoglycemia options, ultimately lowering the projected 1.31 billion global T2D cases by 2050 through sustained, cost-effective management.