International experts have recommended the expanded use of SGLT-2 inhibitors and GLP-1 receptor agonists for all or nearly all adults with type 2 diabetes (T2D), particularly those at higher risk of cardiovascular and kidney complications. Published in The BMJ, these guidelines aim to shift the treatment paradigm beyond glycemic control and assist doctors in making better decisions with their patients. The recommendations are based on the latest evidence, utilize the GRADE approach for assessing evidence quality, and are supported by an interactive decision aid. The findings stem from a comprehensive living systematic review and network meta-analysis of nearly half a million adults with T2D across 869 randomized controlled trials, covering 63 medications and 26 patient-important outcomes.

For individuals at lower risk, the panel advises against routine recommendation, suggesting instead a discussion of treatment options with patients, noting that decisions are likely to be more contextual and based on individual priorities. For adults with diabetes and chronic kidney disease (CKD) at higher risk, the drug finerenone is suggested as benefits are more likely to outweigh risks, while its use is not recommended for those at moderate risk. For adults with diabetes and obesity, the importance of weight loss alongside cardiovascular and kidney risk reduction is emphasized. Tirzepatide is suggested for its superior weight loss effects, irrespective of the patient's cardiovascular and kidney risk profile. However, when choosing between GLP-1 receptor agonists and tirzepatide, clinicians should weigh the higher certainty of cardiovascular and kidney benefits (offered by GLP-1 receptor agonists) against larger weight loss benefits (offered by tirzepatide), based on a patient's risk profile and their values and preferences.

The panel acknowledges that the lack of availability or high cost of some medications may be prohibitive and impact implementation across different healthcare systems. Senior author Professor Per Olav Vandvik highlights the need for global collaboration on living evidence to inform policy and practice, similar to efforts during COVID-19. The authors encourage the reuse, adaptation, and translation of these living guidelines through global initiatives such as the Alliance for Living Evidence (ALIVE) and the Evidence Synthesis Infrastructure Collaborative (ESIC). The panel commits to regular updates of recommendations in parallel with evidence updates.

Market Signals

Sector Impact & Opportunities: Recommendations signal a paradigm shift in T2D treatment, prioritizing cardiovascular and renal protection. This will drive market growth for SGLT-2 inhibitors and GLP-1 receptor agonists, with opportunities for expanded prescribing and market share gains.
Competitor Positioning: Major pharmaceutical players in the diabetes drug market (e.g., Novo Nordisk, Eli Lilly, AstraZeneca, Sanofi) are poised to leverage these recommendations to boost their portfolios in these drug classes.
Price Movements & Volatility: While these newer drugs carry higher costs, the enhanced clinical benefits are expected to support increased uptake and potentially influence pricing strategies as demand grows.

Stakeholder Impact

Winners: Pharmaceutical companies manufacturing SGLT-2 inhibitors and GLP-1 receptor agonists; patients with T2D, especially those at high cardiovascular and renal risk; healthcare providers gaining access to improved treatment options. Losers: Manufacturers of older diabetes medications; the healthcare system in the short term due to higher drug costs, though long-term savings from complication reduction are anticipated.

Action Timeline

Immediate (24-48h): Pharmaceutical companies should assess the impact of recommendations on their product portfolios and adapt marketing strategies accordingly.
Short-term (1-2 weeks): Focus on educating healthcare professionals about the expanded benefits of these drug classes and navigating regulatory/reimbursement requirements (e.g., PBS in Australia).
Long-term: Monitor changes in PBS listings, updates to clinical guidelines, new clinical trial results, and competitor product developments.

Risk Assessment

Regulatory Risks: Ensuring marketing and supply through approved channels, mindful of regulatory scrutiny (e.g., TGA's focus on illegal compounding in Australia).
Market Volatility: The higher cost of these medications compared to older alternatives remains a potential barrier, requiring careful market access strategies.
Prescribing Practices: Need for robust prescriber education and adherence to guidelines to avoid off-label prescribing, noting issues highlighted in reviews (e.g., DUSC review on GLP-1 RA prescribing in Australia).
Supply Chain: Ensuring a stable and reliable supply is critical amid increasing demand, as evidenced by availability issues with drugs like Ozempic.

Key Indicators

Market/Industry Signal: A significant shift in diabetes management towards prioritizing cardiovascular and renal protection.
Leading Indicators & Data Points: Increasing prescription rates of SGLT-2 inhibitors and GLP-1 receptor agonists; growing use of SGLT-2 inhibitors in non-diabetic patients; enhanced prescribing by cardiologists.

Regional Perspective

In Australia, these international recommendations align with recent national guidelines, which include SGLT-2 inhibitors as a second-line therapy and recommend them for secondary cardiovascular prevention and delaying CKD progression. The increasing use of SGLT-2 inhibitors in non-diabetic patients and by cardiologists offers unique market insights for Australia. However, the lack of current PBS subsidy for combination therapy (GLP-1 RA with SGLT-2 inhibitors) for diabetes management may create cost barriers for patients.

What to Watch

PBS Listing Changes: Any further expansions to PBS listings for SGLT-2 inhibitors and GLP-1 receptor agonists, particularly for combination therapies or expanded indications.
Guideline Updates: Tracking updates from bodies like the Australian Diabetes Society (ADS) and the Royal Australian College of General Practitioners (RACGP).
Clinical Trial Results: New clinical trial data supporting the expanded use of these drug classes in various patient populations.
Competitor Product Launches: Monitoring new SGLT-2 inhibitor or GLP-1 receptor agonist products entering the Australian market.

Analysis

The international expert recommendations signal a significant evolution in the management of type 2 diabetes, emphasizing cardiovascular and renal protection. This presents a substantial opportunity for pharmaceutical companies with strong portfolios in SGLT-2 inhibitor and GLP-1 receptor agonist classes. However, challenges related to drug cost, accessibility, and the need for clinician education will be critical for successful implementation. The long-term benefits, such as reduced hospitalizations and complications, may outweigh the initial higher costs, but successful adoption hinges on the ability of healthcare systems to adapt and integrate these advanced therapies while considering individual patient preferences.