Now and Next in Type 2 Diabetes

Type 2 diabetes, the most common form of diabetes, affects more than 800 million adults worldwide. People with type 2 diabetes show hyperglycaemia as a result of insulin resistance, and impairment in insulin and glucagon secretion. If type 2 diabetes isn’t well controlled, people can develop microvascular, macrovascular and neuropathic complications, resulting in retinal, renal, neuropathic and vascular disease, along with autonomic and peripheral nerve damage. Type 2 diabetes has societal, environmental and genetic risk factors, and its numbers are rising in children and adolescents. [1-3]

According to Precedence Research, the worldwide type 2 diabetes market is expected to hit $40.1 billion in 2025, rising to $76.4 billion by 2034. The North American market makes up around 36% of the total market, the largest market share overall. Sales for diabetes treatment constitute more than three quarters of the metabolic disorders market. [4]

Management and treatment approaches

The aim for type 2 diabetes is to manage blood glucose levels. The NICE guidelines in the UK suggest an individualised approach based on needs and circumstances, supported by patient education. The recommendations include: [5]

· Healthy eating, exercise, weight loss and stopping smoking

· Diagnosing and managing hypertension

· Monitoring HbA1c and setting an individualised target

· Blood glucose monitoring – self-monitoring or intermittently scanned/real-time continuous glucose monitoring

· Drug treatment:

    o First-line – metformin, SGLT2 inhibitors

    o Further treatment options – DPP 4 inhibitors, pioglitazone, sulfonylureas, insulin

· Managing complications, such as periodontitis, gastroparesis, neuropathy, foot problems, chronic kidney disease, erectile dysfunction, eye disease and cardiovascular disease.

Glucose control can be improved by the use of continuous glucose monitoring (CGM) with both insulin and non-insulin therapies, and automated insulin delivery systems with associated CGM. Early good blood glucose control reduces the risk of diabetic complications in type 2 diabetes. A 24-year follow up of a 20-year trial of intensive blood control with oral sulfonylurea or insulin injections following diagnosis showed 10% fewer deaths, 17% fewer heart attacks, and 26% fewer diabetic complications. Using metformin resulted in 31% fewer heart attacks and 20% fewer deaths. [6] 

Moving prescribing from a glucose-centric focus to a complication-centric focus, where interventions are tailored to managing co-morbid conditions, may help the outcomes for patients with type 2 diabetes. [7] 

New approaches in Type 2 diabetes

GLP-1 agonists have proved highly successful in the treatment of type 2 diabetes, with sales estimated to reach $174.7 billion worldwide by 2035, more than double those in 2024, according to S&P Global; this covers obesity as well as diabetes indications. Leading drugs include Mounjaro (Eli Lilly’s tirzepatide) and Ozempic/Rybelsus (Novo Nordisk’s semaglutide). The companies developing the next-generation GLP-1 drugs, in Phase 2 and Phase 3 development, include: [8]

· Zealand Pharma

· Pfizer

· Amgen

· Structure Therapeutics

· Altimmune

· Viking Therapeutics

· Merck  

· Roche/Genentech

· AstraZeneca

· Terns Pharma

Insulin treatment plays an important role in treating type 2 diabetes, but it comes with a risk of hypoglycaemic episodes, which are associated with unpleasant side effects such as confusion, anxiety, and weakness, or even seizures, unconsciousness and death. To meet this need, glucose-sensitive treatments have been sought for decades. As an example, researchers at Novo Nordisk are developing NNC2215, a modified insulin molecule that incorporates a glucose-sensitive switch. When glucose levels are low, the insulin remains inactive; when glucose levels rise, the insulin is activated. This molecule is in preclinical trials, and the approach has potential to improve outcomes and reduce adverse effects and complications for patients with type 2 diabetes. [9]

The effectiveness of glucose lowering drugs varies from person to person. Researchers at the University of Exeter, UK, have developed a tool that can identify the most effective glucose-lowering drugs after metformin for treatment of an individual with type 2 diabetes. The five-drug class model, which is based on observational data, uses nine routinely available clinical features of people with type 2 diabetes at drug initiation as predictive factors. [10, 11]

Combining a number of therapeutics with different mechanisms of action is already an accepted approach to the treatment of type 2 diabetes. Researchers have combined a GLP-1 agonist, exendin-4, with a DYRK1A kinase inhibitor, harmine, in mouse models and shown that this improved beta cell numbers, beta cell function and glycaemic control. While this is only preclinical development it could support regenerative medicine approaches in the future. [12]

Insulin has to be delivered as an injection, and this can be a challenge for many patients, reducing its uptake as an effective treatment in Type 2 diabetes. The idea of oral insulin has been discussed for over a century, with the first (unsuccessful) attempts in 1922 and 1923. Insulin is a protein and is vulnerable to chemical and enzymatic breakdown in the gastrointestinal tract. Any insulin that survives face absorption challenges in the gut. [13, 14]

No oral insulins have yet been launched, but potential approaches to stabilise or protect the insulin and improve its uptake include: [14]

· Nanoformulations – liposomes, metallic, polymeric and silicone nanoparticles, quantum dots

· Microparticles

· Hydrogels

· Solid oral dosage forms

· Modified insulin

Cell-associated therapies are offering promise for the treatment of type 2 diabetes. ReCET (Re-Cellularization via Electroporation Therapy) uses pulsed electrical fields to regenerate cells in the gut in order to improve sensitivity to endogenous insulin. In a trial carried out by the Amsterdam University Medical Centre, patients with type 2 diabetes and a BMI of 24-40 underwent the ReCET procedure. They had a two-week isocaloric diet and then started taking the GLP-1 agonist semaglutide. Over two years, 12 of 14 participants (86%) no longer needed to take insulin, and there were no serious adverse effects. A larger randomised study, EMINENT-2, is under way, comparing ReCET with a sham procedure. [15-17] In 2024, a Chinese case study reported the first-in-human tissue replacement therapy using intrahepatic implantation of islet tissue differentiated in vitro from autologous endoderm stem cells. The patient, who had type 2 diabetes and impaired islet function, was able to discontinue insulin, acarbose and metformin, and had significant improvements in glycaemic control at 27 months. Further studies will be needed. [18]

Artificial intelligence (AI) has potential to improve the outcomes in type 2 diabetes. It can make drug discovery and development more efficient, accurate, faster and more cost effective. It has potential in the prediction of onset, management of risk factors, screening, disease classification, health education, diet monitoring and recommendations, blood glucose monitoring, detection of adverse effects and optimising treatment regimens. One example of its use is the development of a voice-based algorithm as a screening tool. [19, 20]

The future in type 2 diabetes

The global growth of type 2 diabetes, and its impact on individual patients and on healthcare provision, must be tackled from a number of directions: prevention through lifestyle changes, early diagnosis, effective treatment and close monitoring. Pharma, biotech, medtech and AI companies can play a powerful and positive role, from prevention to management.

References:

1. Goyal, S. and V. Vanita, The Rise of Type 2 Diabetes in Children and Adolescents: An Emerging Pandemic. Diabetes Metab Res Rev, 2025. 41(1): p. e70029.

2. Robertson, R.P. and K.J. Lipska, Type 2 diabetes mellitus: Prevalence and risk factors. UpToDate, 4 March 2025 2025. Available from: https://www.uptodate.com/contents/type-2-diabetes-mellitus-prevalence-and-risk-factors.

3. Khardori, R., Type 2 Diabetes Mellitus. Medscape, 16 December 2024. Available from: https://emedicine.medscape.com/article/117853-overview.

4. Type 2 Diabetes Market Size, Share, and Trends 2025 to 2034. Precedence Research. 2025. Available from: https://www.precedenceresearch.com/type-2-diabetes-market#.

5. Type 2 diabetes in adults: management (NICE guideline NG28). Last accessed: 29 June 2022. Available from: https://www.nice.org.uk/guidance/ng28.

6. Adler, A.I., et al., Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91). Lancet, 2024. 404(10448): p. 145-155.

7. Schwartz, S.S. and M.E. Herman, Gluco-regulation & type 2 diabetes: entrenched misconceptions updated to new governing principles for gold standard management. Front Endocrinol (Lausanne), 2024. 15: p. 1394805.

8. Jasuja, R. Visible Alpha GLP-1 Drug Monitor: The Emerging Pipeline. S&P Global Market Intelligence. Last accessed: 26 July 2024. Available from: https://visiblealpha.com/blog/visible-alpha-glp-1-drug-monitor-the-emerging-pipeline/.

9. Hoeg-Jensen, T., et al., Glucose-sensitive insulin with attenuation of hypoglycaemia. Nature, 2024. 634(8035): p. 944-951.

10. Dennis, J.M., et al., A five-drug class model using routinely available clinical features to optimise prescribing in type 2 diabetes: a prediction model development and validation study. Lancet, 2025. 405(10480): p. 701-714.

11. UK innovation offers major opportunity to transform treatment for people with type 2 diabetes worldwide. NIHR: Exeter Biomedical Research Centre. Last accessed: 25 February 2025. Available from: https://www.exeterbrc.nihr.ac.uk/news/uk-innovation-offers-major-opportunity-to-transform-treatment-for-people-with-type-2-diabetes-worldwide/.

12. Rosselot, C., et al., Harmine and exendin-4 combination therapy safely expands human beta cell mass in vivo in a mouse xenograft system. Sci Transl Med, 2024. 16(755): p. eadg3456.

13. Kalra, S., B. Kalra, and N. Agrawal, Oral insulin. Diabetol Metab Syndr, 2010. 2: p. 66.

14. Low, C.Y., et al., Critical updates on oral insulin drug delivery systems for type 2 diabetes mellitus. J Nanobiotechnology, 2025. 23(1): p. 16.

15. Smart insulin and stem cell transplants: Research Highlights October 2024. Diabetes UK. Last accessed: 30 October 2024. Available from: https://www.diabetes.org.uk/about-us/news-and-views/smart-insulin-and-stem-cell-transplants-research-highlights-october-2024.

16. Novel diabetes treatment shows promise in eliminating insulin dependency. Middle East Health, 12 December 2024. Available from: https://middleeasthealth.com/medical-specialty-features/diabetes/novel-diabetes-treatment-shows-promise-in-eliminating-insulin-dependency/.

17. Busch, C.B.E., et al., Recellularization via electroporation therapy of the duodenum combined with glucagon-like peptide-1 receptor agonist to replace insulin therapy in patients with type 2 diabetes: 12-month results of a first-in-human study. Gastrointest Endosc, 2024. 100(5): p. 896-904.

18. Wu, J., et al., Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue. Cell Discov, 2024. 10(1): p. 45.

19. Elbeji, A., et al., A voice-based algorithm can predict type 2 diabetes status in USA adults: Findings from the Colive Voice study. PLOS Digit Health, 2024. 3(12): p. e0000679.

20. Guan, Z., et al., Artificial intelligence in diabetes management: Advancements, opportunities, and challenges. Cell Rep Med, 2023. 4(10): p. 101213.