Bayer's FOUNTAIN Study Reveals Persistent Risks in Chinese Diabetes Patients Despite Advanced Treatments

What Does Bayer's FOUNTAIN Study Reveal About Diabetes Management?

Bayer's FOUNTAIN platform study has revealed significant real-world data on SGLT2 inhibitor and GLP-1 receptor agonist use among Chinese patients with type 2 diabetes and chronic kidney disease. Analyzing 935 SGLT2i users and 4,821 GLP-1 RA users from the Tianjin Healthcare and Medical Big Data Platform, researchers documented substantial residual risks of kidney failure and cardiovascular events despite current treatments, highlighting the need for improved disease management strategies.

The retrospective observational study, conducted between 2012-2019, represents the largest standardized analysis of its kind in mainland China. Patient data was rigorously standardized according to the Observational Medical Outcomes Partnership (OMOP) common data model, ensuring analytical reliability across the cohorts. The study specifically targeted new users of these medication classes with at least 12 months of continuous enrollment in the database prior to treatment initiation, excluding patients with type 1 diabetes, kidney cancer, or kidney failure at baseline. The researchers tracked clinical outcomes until treatment discontinuation, development of kidney failure, end of the study period, or death.

Demographic analysis revealed similar patterns between the two cohorts, with mean ages of 59.1 years for SGLT2i users and 55.7 years for GLP-1 RA users. Both groups had slightly higher proportions of male patients (61.4% for SGLT2i and 55.7% for GLP-1 RA) and similar durations of T2D (approximately 5 years) and CKD (approximately 3 years). Notably, metformin was the most commonly prescribed treatment during the baseline period (63.1% for SGLT2i cohort; 73.2% for GLP-1 RA cohort), followed by alpha-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors. Insulin use was recorded for 73% and 80% of patients in the respective cohorts. The disease burden was substantial, with nephropathy, cardiovascular disease, and peripheral vascular disease being the most common complications. The mean baseline estimated glomerular filtration rate (eGFR) was 90.6 mL/min/1.73 m² for SGLT2i users and 97.2 mL/min/1.73 m² for GLP-1 RA users, suggesting that most patients had early-stage CKD when initiating these treatments.

Healthcare resource utilization patterns revealed a strong preference for specialist care over primary care visits, with over 96% of patients having at least one specialist visit during the baseline period compared to only about 25% having general practitioner visits. During follow-up, the trend continued with approximately 80% of patients in both cohorts maintaining specialist care. This reflects China's healthcare system structure during the study period, which preceded the full implementation of tiered medical systems emphasized in national guidelines released in 2015 and regional plans established in 2017. Regular monitoring of kidney function appeared suboptimal, with only about 50% of patients having follow-up eGFR measurements and even fewer having urinary albumin-to-creatinine ratio assessments.

Is Residual Clinical Risk a Call for Integrated Care?

The study's most concerning finding was the substantial incidence of serious clinical outcomes despite treatment. In the SGLT2i cohort, the incidence rates per 100 person-years were 3.1 for kidney failure and 36.4 for acute coronary syndrome. The GLP-1 RA cohort showed rates of 4.9 for kidney failure and 12.4 for acute coronary syndrome. These findings align with previous research from Hong Kong showing similar kidney outcome incidence rates, but highlight the persistent cardiovascular risk in this population. "This underscores the need for a more comprehensive and integrated approach to disease management, including efficient intervention and proactive monitoring," the researchers noted, pointing to the potential value of combination therapies including newer agents like non-steroidal mineralocorticoid receptor antagonists.

The mechanisms behind these outcomes merit consideration. SGLT2 inhibitors function by blocking glucose reabsorption in the renal tubule, while GLP-1 receptor agonists enhance insulin secretion and suppress glucagon release. Clinical trials like DAPA-CKD and CREDENCE have demonstrated the renal protective effects of SGLT2i, while analyses from the REWIND and LEADER trials have suggested similar benefits for GLP-1 RAs. Despite these established mechanisms, the residual risk observed in this real-world population suggests that current monotherapies may be insufficient for comprehensive cardiorenal protection in high-risk patients with both T2D and CKD.

Of the eligible patients identified in the Tianjin database, only a small proportion met the study criteria – 0.36% for SGLT2i and 4.01% for GLP-1 RA. This low inclusion rate was primarily due to the timing of drug launches in China, with most SGLT2i agents entering the market after 2017 and most GLP-1 RAs (except liraglutide) launching after 2018. The 12-month washout requirement further limited the eligible population. This context is important for understanding the study's representation of early adopters of these medication classes in China.

Study limitations include its regional nature, potentially limiting generalizability to broader Chinese populations, relatively short follow-up periods, and the inability to capture medication adherence based solely on prescription data. The study's end date of December 31, 2019, was deliberately set to avoid COVID-19 disruptions but consequently excluded newer treatment options launched after this date. Despite these limitations, the study provides valuable insights into real-world treatment patterns and outcomes in a previously understudied population.

What Future Opportunities Lie Ahead in Diabetes Treatment?

Industry Context: This study emerges amid growing pharmaceutical interest in cardiorenal protection beyond glucose control in diabetes management. The findings reinforce the significant unmet need despite current therapies, potentially accelerating market opportunities for combination approaches and newer drug classes like non-steroidal MRAs. For companies developing treatments for diabetic kidney disease, these real-world data from China—the world's largest diabetes market—provide critical insights for clinical development programs and market access strategies. The study also highlights the evolving landscape of diabetes care in China, where specialist-centered treatment remains dominant despite policy shifts toward tiered healthcare delivery, suggesting potential market gaps in integrated care models that pharmaceutical companies might address through disease management programs alongside drug development.

Summary

Bayer's FOUNTAIN platform study has provided comprehensive real-world evidence on SGLT2 inhibitor and GLP-1 receptor agonist use among Chinese patients with type 2 diabetes and chronic kidney disease, analyzing data from 935 SGLT2i users and 4,821 GLP-1 RA users from the Tianjin Healthcare and Medical Big Data Platform between 2012-2019. The retrospective observational study, representing the largest standardized analysis of its kind in mainland China, revealed substantial residual risks of kidney failure and cardiovascular events despite current treatments, with incidence rates of 3.1 per 100 person-years for kidney failure in the SGLT2i cohort and 4.9 in the GLP-1 RA cohort, alongside significant acute coronary syndrome rates of 36.4 and 12.4 respectively. Demographic analysis showed similar patient profiles across cohorts, with mean ages around 55-59 years, predominantly male patients, and comparable disease durations of approximately 5 years for type 2 diabetes and 3 years for chronic kidney disease. Healthcare utilization patterns revealed a strong preference for specialist care over primary care, with over 96% of patients having specialist visits during baseline, reflecting China's healthcare system structure prior to full implementation of tiered medical systems. The study identified suboptimal kidney function monitoring, with only about 50% of patients receiving follow-up eGFR measurements, and highlighted the persistent cardiovascular and renal risks despite established mechanisms of SGLT2 inhibitors blocking glucose reabsorption and GLP-1 receptor agonists enhancing insulin secretion. These findings underscore the need for more comprehensive and integrated disease management approaches, including potential combination therapies with newer agents like non-steroidal mineralocorticoid receptor antagonists, and provide critical insights for pharmaceutical companies developing treatments for diabetic kidney disease in China, the world's largest diabetes market.