Breakthrough Clinical Results
Endogenex announced positive 48-week results from its REGENT-1 clinical study at Digestive Disease Week 2025. The study evaluated the safety and efficacy of the ReCET System, a novel endoscopic procedure using pulsed electric fields to treat type 2 diabetes. Results showed significant and durable improvements in insulin sensitivity and beta-cell function, persisting at 48 weeks. The procedure was 100% successful with no serious adverse events. These findings highlight the duodenum as a key therapeutic target for type 2 diabetes treatment and suggest the ReCET System's potential as a transformative therapy.
Key Highlights
- Significant and durable improvements in insulin sensitivity and beta-cell function observed at 48 weeks.
- 100% procedural success rate with no serious adverse events.
- ReCET System, a novel endoscopic procedure using pulsed electric fields, targets the duodenum.
- Results suggest the duodenum is a critical therapeutic target for type 2 diabetes.
Incidence and Prevalence
The most recent estimates for the global incidence and prevalence of Type 2 Diabetes come from the Global Burden of Disease (GBD) 2021 study.
2021 Estimates:
- Prevalence: In 2021, an estimated 529 million people (95% UI 500-564 million) were living with diabetes globally. The global age-standardized prevalence of diabetes was 6.1% (5.8-6.5%). Type 2 diabetes accounted for 96.0% (95.1-96.8%) of all diabetes cases and 95.4% (94.9-95.9%) of diabetes-related DALYs (Disability-Adjusted Life Years) worldwide.
- Incidence: While the provided source doesn't explicitly state the total incidence for 2021, it mentions that type 2 diabetes is the predominant form of diabetes, representing the vast majority of cases. Therefore, the overall diabetes incidence would largely reflect the incidence of type 2 diabetes.
- Regional Variations: The highest age-standardized diabetes prevalence rates were in North Africa and the Middle East (9.3%, 8.7-9.9%) and Oceania (12.3%, 11.5-13.0%). Qatar had the highest age-specific prevalence (76.1%, 73.1-79.5% in those aged 75-79 years).
Trends and Projections:
- Increasing Burden: Multiple studies confirm a consistent upward trend in the global burden of type 2 diabetes since 1990. This increase is particularly pronounced in low- and middle-SDI regions, driven by population growth and epidemiological shifts (changes in lifestyle, diet, etc.). High-SDI countries also experience an increase, though at a slower rate, primarily influenced by population aging.
- Future Projections: Projections estimate that by 2050, over 1.31 billion people (1.22-1.39 billion) will be living with diabetes, with age-standardized prevalence exceeding 10% in North Africa and the Middle East (16.8%, 16.1-17.6%) and Latin America and the Caribbean (11.3%, 10.8-11.9%).
Specific Age Groups:
- Adolescents and Young Adults (10-24 years): The incidence of type 2 diabetes in this age group has more than doubled between 1990 and 2021, rising from 56.02 to 123.86 per 100,000 population. Oceania had the highest incidence rates in 2021, while North Africa and the Middle East showed the fastest increases.
- Early-Onset T2DM (15-34 years): Incidence and prevalence have risen significantly worldwide, especially in high-SDI regions. While global mortality and DALYs seem stable, low-SDI regions show concerning increases.
Key Factors:
- High BMI: A major driver of type 2 diabetes, accounting for over half of global type 2 diabetes DALYs in 2021. Its contribution has increased substantially since 1990.
- Low Physical Activity: The burden of type 2 diabetes attributable to low physical activity has more than doubled since 1990, particularly affecting older adults and those in low-middle and middle-SDI regions.
- Other Risk Factors: Other contributing factors include urbanization, sedentary lifestyles, nutrition transitions (shifts towards processed foods, sugary drinks), and environmental factors like air pollution.
It's crucial to note that these are estimates, and the actual numbers may vary. The data highlights the urgent need for comprehensive public health interventions, including lifestyle modifications, early detection and management, and targeted policies to address the growing diabetes epidemic.
Economic Burden
Diabetes Economic Burden
The economic burden of type 2 diabetes (T2DM) is substantial in both the USA and Europe, although precise estimates vary depending on the year and scope of the study. Here's a summary of some of the latest available data:
USA:
- 2022: The estimated cost of diagnosed diabetes (including both type 1 and type 2) reached $412.9 billion, including $306.6 billion in direct medical costs and $106.3 billion in indirect costs. This represents a 7% increase from 2017 and a 35% increase from 2012 (in 2022 dollars). One in four healthcare dollars in the US is spent on diabetes care, with 61% of that attributable to the disease itself. Per capita, individuals with diabetes incur annual medical expenditures of $19,736, with $12,022 directly attributable to diabetes. This is 2.6 times higher than expenditures without diabetes. Indirect costs stem from reduced employment due to disability ($28.3 billion), presenteeism ($35.8 billion), and lost productivity due to premature deaths ($32.4 billion).
- 2017: The total cost of diagnosed diabetes was estimated at $327 billion, including $237 billion in direct medical costs and $90 billion in reduced productivity. This represented a 26% increase from 2012 due to increased prevalence and cost per person. One in four healthcare dollars was spent on diabetes care, with over half directly attributable to the disease. Average medical expenditures were $16,750 per year ($9,600 attributable to diabetes), 2.3 times higher than without diabetes.
Europe:
European data is often presented on a per-patient basis or aggregated across multiple countries, making direct comparison with US national figures challenging. However, several studies provide insights into the economic burden:
- A 2015 study estimated the global cost of diabetes (all types) at $1.31 trillion, with Europe bearing a significant portion of this burden. While North America had the highest cost relative to GDP, middle-income countries within Europe experienced a larger economic burden as a percentage of GDP compared to high-income European countries.
- A 2019 study on T2DM in adolescents in Western Europe found increasing prevalence and disability, particularly for T2DM compared to T1DM. While specific cost data wasn't provided, the study highlighted the growing burden and need for health system responses.
- A 2021 study estimated the annual cost of cardiovascular disease (a major diabetes complication) across the 27 EU countries at 282 billion (health and long-term care: 155 billion; productivity losses: 48 billion; informal care: 79 billion). The per capita cost was 630, ranging from 381 in Cyprus to 903 in Germany.
Key Cost Drivers:
Across both regions, key cost drivers for T2DM include:
- Direct Medical Costs: Hospital inpatient care, prescription medications (especially for complications), antidiabetic agents, physician visits, and nursing/residential facility stays.
- Indirect Costs: Reduced productivity due to disability, presenteeism, lost workdays, premature mortality, and informal caregiving.
- Complications: The presence and severity of complications significantly increase costs. Cardiovascular disease, nephropathy, retinopathy, neuropathy, and foot ulcers are major contributors.
Conclusion:
T2DM imposes a massive and growing economic burden on both the USA and Europe. The costs are driven by a combination of direct medical expenses, lost productivity, and the high prevalence of costly complications. Effective prevention and management strategies are crucial to mitigate this burden and improve patient outcomes.
Study Design Parameters
Several studies have explored various interventions for Type 2 Diabetes (T2D), employing diverse study designs and endpoints. Here's a summary of key trials:
1. Interventions Targeting Glycemic Control and Weight Loss:
- EMPA-REG OUTCOME: This study investigated the impact of empagliflozin on adults with T2D and high cardiovascular risk. The primary endpoint was a composite of decline in estimated glomerular filtration rate (eGFR) (thresholds of ≥30%, ≥40%, ≥50%, or ≥57%), initiation of renal replacement therapy (RRT), or renal death. Empagliflozin significantly lowered the risk for each composite endpoint. A 40% decline in eGFR, combined with ESKD or renal death, was suggested as a reliable alternative to the traditional 57% decline.
- TIMES 2: This phase 3 trial evaluated imeglimin as monotherapy or combination therapy in Japanese patients with T2D. The primary endpoint was safety, while secondary endpoints included changes in HbA1c and fasting plasma glucose at week 52. Imeglimin demonstrated long-term safety and efficacy in both monotherapy and combination therapy.
- PIONEER 1: This phase 3a trial compared oral semaglutide with placebo in patients with T2D managed by diet and exercise. Primary endpoint was change in HbA1c at week 26, with a confirmatory secondary endpoint of body weight change. Oral semaglutide showed superior improvements in HbA1c and body weight compared to placebo.
- Head-to-Head Comparison of Oral Semaglutide and Empagliflozin: This 52-week trial compared oral semaglutide 14 mg with empagliflozin 25 mg in patients with T2D uncontrolled on metformin. The primary endpoint was change in HbA1c at week 26, and a key secondary endpoint was body weight change. Oral semaglutide showed superior HbA1c reduction but not weight loss at 26 weeks, with significant improvements in both at 52 weeks.
- Trial Comparing Semaglutide and Dulaglutide: This phase 3 trial compared tirzepatide (5, 10, and 15 mg) with dulaglutide (0.75 mg) in Japanese patients with T2D. The primary endpoint was the mean change in HbA1c from baseline at week 52. Tirzepatide demonstrated superior glycemic control and body weight reduction compared to dulaglutide.
2. Trials Investigating Cardiovascular and Renal Outcomes:
- Cardiovascular Outcomes Trials (CVOTs): Several CVOTs have been conducted to assess the cardiovascular safety and efficacy of glucose-lowering drugs. These trials often use composite endpoints such as major adverse cardiovascular events (MACE), cardiovascular death, and hospitalization for heart failure. Some SGLT2 inhibitors and GLP-1 RAs have shown cardiovascular benefits in these trials.
- CREDENCE: This trial compared canagliflozin with placebo in patients with T2D and established kidney disease. The primary composite endpoint included end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. Canagliflozin significantly reduced the risk of the primary composite outcome.
- DAPA-CKD: This trial evaluated dapagliflozin in patients with chronic kidney disease (CKD), with and without T2D. The primary composite endpoint included a decline in eGFR, end-stage kidney disease, or death from renal or cardiovascular causes. Dapagliflozin significantly reduced the risk of the primary outcome.
3. Trials Focusing on Lifestyle Interventions:
- Look AHEAD: This trial assessed the long-term effects of an intensive lifestyle intervention (diet and exercise) compared to diabetes support and education in overweight or obese individuals with T2D. The primary outcome was time to a major cardiovascular event.
- DIADEM-I: This trial compared an intensive lifestyle intervention using a low-energy diet and physical activity with usual medical care in young individuals with early T2D. The primary outcome was weight loss at 12 months.
- X-PERT: This trial evaluated a structured education programme for patients with T2D compared to usual care. The primary outcome was HbA1c at 1 year.
4. Trials with Other Objectives:
- ASPEN: This trial investigated the effect of atorvastatin on CVD prevention in subjects with T2D and low LDL cholesterol levels. The primary composite endpoint included cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and other cardiovascular events.
- CARMELINA: This trial evaluated linagliptin on CV and kidney outcomes in T2D patients at high risk. The primary outcome was time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke.
- SMARTEST: This trial compares dapagliflozin and metformin as first-line T2D medication regarding the development of complications. The primary endpoint is a composite of all-cause death, MACE, and microvascular complications.
These trials represent a selection of the research conducted on T2D. The specific design parameters and endpoints vary depending on the research question and the intervention being studied. It is important to consider the specific context of each trial when interpreting the results.
