Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder affecting millions of adults worldwide, requiring individualized treatment approaches that balance glycemic control, cardiovascular risk reduction, weight management, and quality of life. The National Institute for Health and Care Excellence (NICE) guideline NG28, updated in 2026, provides comprehensive recommendations for healthcare professionals on selecting, reviewing, and modifying glucose-lowering therapies in adults with type 2 diabetes.
This article presents a detailed analysis of the 2026 update, emphasizing the principles of patient-centred care, shared decision-making, and the integration of cardiovascular and renal protection into treatment algorithms. We explore key recommendations regarding metformin optimization, the role of newer agents (SGLT-2 inhibitors and GLP-1 receptor agonists), management of comorbidities, and criteria for treatment modification or discontinuation.
1. Introduction: The Evolving Landscape of Type 2 Diabetes Management
Type 2 diabetes mellitus is a chronic metabolic condition characterized by insulin resistance and progressive beta-cell dysfunction, leading to hyperglycemia and increased risk of microvascular and macrovascular complications. The global prevalence of diabetes continues to rise, with an estimated 537 million adults affected worldwide as of 2021, a number projected to reach 783 million by 2045 .
The management of type 2 diabetes has evolved dramatically over the past two decades. Traditional approaches focused primarily on glycaemic control measured by HbA1c. However, contemporary treatment paradigms recognize the importance of:
- Cardiovascular risk reduction
- Renal protection
- Weight management
- Quality of life
- Patient preferences and values
The National Institute for Health and Care Excellence (NICE) guideline NG28, updated in 2026, reflects this evolution, providing evidence-based recommendations for choosing, reviewing, and changing medicines in adults with type 2 diabetes. This article provides a comprehensive analysis of the 2026 update, offering practical guidance for healthcare professionals implementing these recommendations.
2. Foundational Principles: Diet, Healthy Living, and Patient Engagement
2.1 The Cornerstone of Diabetes Management
The NICE guideline emphasizes that pharmacological therapy must be built upon a foundation of diet and healthy living advice. At each point in the treatment journey, clinicians should reinforce advice about:
| Component | Key Elements |
|---|---|
| Dietary Management | Individualized nutritional advice; emphasis on whole foods, fibre, and healthy fats |
| Physical Activity | Regular exercise tailored to patient capabilities and preferences |
| Weight Management | Referral to NICE guideline on overweight and obesity; weight loss targets |
| Behavioural Support | Ongoing encouragement and problem-solving |
| Resources | NHS Better Health website and other trusted patient resources |
Clinical Implication: Pharmacotherapy should never be viewed as a substitute for lifestyle modification. Rather, medications are adjuncts that support patients in achieving and maintaining optimal health outcomes.
2.2 Involving People in Medicine Discussions
A central theme of the 2026 update is shared decision-making. Healthcare professionals must engage patients as active partners in treatment decisions, supporting them to make informed choices about their care .
2.2.1 Factors to Discuss with Patients
When discussing medicine treatment options, clinicians should address:
| Factor | Clinical Considerations |
|---|---|
| Effect on HbA1c | Expected reduction; time to effect; impact on glycemic targets |
| Effect on Weight | Weight-neutral, weight-loss promoting, or weight-gain associated agents |
| Cardiovascular Protection | Evidence for CV outcome benefits (particularly SGLT-2 inhibitors, GLP-1 agonists) |
| Renal Protection | Nephroprotective effects (particularly SGLT-2 inhibitors) |
| Contraindications | Conditions that preclude specific agents (e.g., pioglitazone contraindicated in heart failure) |
| Cost Considerations | When multiple equally suitable medicines exist, use the least expensive |
| Adverse Effects | Common and serious side effects; impact on quality of life |
| Administration | Oral vs. injectable; dosing frequency; device usability |
| Patient Preferences | Values, priorities, and concerns about treatment |
2.3 Managing Multiple Comorbidities
Many adults with type 2 diabetes have multiple comorbidities, creating complexity in treatment decisions. The guideline provides specific guidance for these situations :
“If a person has more than one comorbidity (for example, atherosclerotic cardiovascular disease and obesity), make a shared decision with them about which comorbidity to prioritise when choosing medicines.”
Priority Considerations:
| Priority | Examples |
|---|---|
| Cardiovascular Protection | Subcutaneous semaglutide (Ozempic) for people with atherosclerotic cardiovascular disease |
| Renal Protection | SGLT-2 inhibitors for people with chronic kidney disease |
| Contraindications | Metformin contraindicated when eGFR <30 mL/min/1.73m² |
| Frailty | Special considerations for older adults with frailty (see frailty section in full guideline) |
| Drug Interactions | Review all concomitant medications and doses |
2.4 Sick Day Rules
The guideline emphasizes providing clear sick day rules in each person’s individualized treatment plan. These rules typically include:
- When to temporarily stop certain medications (e.g., SGLT-2 inhibitors, metformin)
- Increased monitoring of blood glucose
- When to seek medical advice
- Hydration recommendations
- Medication adjustments during illness
3. Reviewing Medicines: A Systematic Approach
3.1 Principles of Medicine Review
When reviewing treatments, the guideline emphasizes shared decision-making and a systematic approach before considering treatment changes :
| Step | Action |
|---|---|
| 1. Optimize Current Regimen | Ensure existing treatments are optimized before switching or adding new agents |
| 2. Assess Contributing Factors | Review adverse effects, prescribed doses, formulations, and adherence |
| 3. Revisit Lifestyle Advice | Reinforce diet and healthy living recommendations |
| 4. Consider Diagnosis | If response suggests type 1 diabetes, revisit initial diagnosis (see NICE guideline on type 1 diabetes) |
| 5. Evaluate Goal Achievement | If individualised glycemic and weight targets are met, consider continuing successful therapies |
3.2 Specific Considerations for Continuing Medications
3.2.1 SGLT-2 Inhibitors for Cardiovascular and Renal Protection
A key recommendation in the 2026 update is:
“Consider continuing SGLT-2 inhibitors for their cardiovascular or renal benefits, even if they do not help the person reach their individualised glycemic targets.”
Rationale: SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin) have demonstrated significant cardiovascular and renal benefits in large outcome trials, independent of their glucose-lowering effects. These benefits include:
| Benefit | Evidence |
|---|---|
| Heart Failure Hospitalization | Reduced risk of hospitalization for heart failure |
| Cardiovascular Death | Reduced risk of CV mortality in some trials |
| Major Adverse Cardiovascular Events (MACE) | Benefits in patients with established CVD |
| Renal Outcomes | Slowed progression of diabetic kidney disease |
| All-Cause Mortality | Reduced mortality in some populations |
Clinical Implication: Even if HbA1c targets are not fully achieved, continuing SGLT-2 inhibitors may provide life-prolonging benefits that justify their ongoing use.
3.2.2 Metformin Optimization
For patients already on standard-release metformin:
“Continue standard-release metformin if it is effective. Switch to modified-release metformin if standard-release metformin is not tolerated, or this is the person’s preference.”
Practical Considerations:
| Formulation | Characteristics | Indication |
|---|---|---|
| Standard-Release Metformin | Multiple daily dosing; higher GI side effect profile | First-line; effective and well-tolerated |
| Modified-Release Metformin | Once-daily dosing; improved GI tolerability | Intolerance to standard-release; patient preference |
3.3 Criteria for Discontinuing Medications
3.3.1 GLP-1 Receptor Agonists and Tirzepatide
The guideline provides specific criteria for stopping GLP-1 receptor agonists or tirzepatide:
“Stop GLP-1 receptor agonists or tirzepatide if:
- the person becomes underweight (BMI under 18.5 kg/m²), or
- they do not help the person reach their individualised glycemic targets and they are not being taken for their cardiovascular benefits.”
Rationale: GLP-1 receptor agonists and tirzepatide (a dual GIP/GLP-1 receptor agonist) promote weight loss as part of their mechanism of action. While beneficial for overweight/obese patients, continued use in underweight individuals may be harmful. Additionally, these agents should demonstrate meaningful glycemic benefit unless being used specifically for cardiovascular protection.
3.3.2 Combination Restrictions
“Do not offer a GLP-1 receptor agonist or tirzepatide and a DPP-4 inhibitor together to treat type 2 diabetes.”
Rationale: Both drug classes target the incretin pathway, with GLP-1 agonists providing exogenous GLP-1 receptor activation and DPP-4 inhibitors preventing endogenous GLP-1 degradation. Combining these agents offers limited additional benefit while increasing cost and potential side effects, without established additive efficacy.
4. Practical Implementation Guide
4.1 Algorithm for Treatment Selection and Review
The following algorithm synthesizes NICE recommendations into a practical clinical pathway:
Step 1: Foundational Interventions
- Diet and healthy living advice
- Weight management support
- Patient education
Step 2: Initial Pharmacotherapy
- Metformin (standard-release or modified-release based on tolerance)
- Consider SGLT-2 inhibitors early if cardiovascular/renal protection needed
Step 3: Review and Optimization
- Assess adherence, tolerability, glycemic response
- Optimize doses
- Revisit lifestyle advice
Step 4: Intensification (if targets not met)
- Add second agent based on patient characteristics:
- If CVD/renal disease: SGLT-2 inhibitor or GLP-1 agonist
- If obesity: GLP-1 agonist or tirzepatide (weight-loss promoting)
- If cost concerns: sulfonylurea or pioglitazone (contraindications apply)
Step 5: Ongoing Review
- Continue effective therapies
- Consider continuing SGLT-2 inhibitors even if glycemic targets not fully met (for CV/renal protection)
- Stop GLP-1 agonists if underweight or no glycemic/CV benefit
- Avoid GLP-1/DPP-4 combinations
4.2 Clinical Decision-Making Framework
| Patient Characteristic | Preferred Agents | Agents to Avoid/Use Cautiously |
|---|---|---|
| Atherosclerotic CVD | SGLT-2 inhibitors, GLP-1 agonists (semaglutide) | Pioglitazone (fluid retention) |
| Heart Failure | SGLT-2 inhibitors | Pioglitazone (contraindicated); saxagliptin (increased HF risk) |
| CKD (eGFR 30-60) | SGLT-2 inhibitors (with eGFR restrictions), GLP-1 agonists | Metformin (dose adjust/caution); sulfonylureas (hypoglycemia risk) |
| CKD (eGFR <30) | Insulin, linagliptin, repaglinide | Metformin (contraindicated); most SGLT-2 inhibitors (contraindicated) |
| Obesity (BMI >30) | GLP-1 agonists, tirzepatide, SGLT-2 inhibitors | Sulfonylureas, insulin (weight gain) |
| Frailty/Elderly | DPP-4 inhibitors, low-dose sulfonylureas | Long-acting sulfonylureas (hypoglycemia risk); aggressive targets |
| Cost-Sensitive Settings | Metformin, sulfonylureas, pioglitazone | Newer, more expensive agents (unless compelling indication) |
5. Special Populations and Considerations
5.1 Frailty in Older Adults
The guideline references specific recommendations for people with frailty in the initial medicines section. Key considerations include:
| Consideration | Rationale |
|---|---|
| Less Stringent Glycaemic Targets | Avoid hypoglycemia; focus on symptom control |
| Simplified Regimens | Improve adherence; reduce treatment burden |
| Avoid High-Risk Agents | Long-acting sulfonylureas; agents with orthostatic hypotension risk |
| Monitor Functional Status | Assess impact of medications on physical and cognitive function |
5.2 Pregnancy and Contraception
While not detailed in this visual summary, the full NICE guideline addresses:
- Pre-conception counselling
- Contraception advice for women of childbearing potential
- Medication safety in pregnancy (typically insulin remains preferred)
5.3 Cultural and Ethnic Considerations
- Awareness of differential cardiovascular risk in South Asian, African-Caribbean populations
- Dietary counseling sensitive to cultural food practices
- Language and health literacy considerations in education
6. Monitoring and Follow-Up
6.1 Key Monitoring Parameters
| Parameter | Frequency | Target/Rationale |
|---|---|---|
| HbA1c | 3-6 monthly | Individualized targets |
| Weight/BMI | Each review | Monitor weight effects of medications |
| Renal Function (eGFR, UACR) | Annually (more often if on SGLT-2 inhibitors or CKD) | Monitor for decline; SGLT-2 initiation requires stable eGFR |
| Cardiovascular Risk Factors | Annually | Blood pressure, lipids |
| Adverse Effects | Each contact | GI symptoms, hypoglycemia, genital infections (SGLT-2 inhibitors) |
| Treatment Burden | Each review | Injection site reactions, device usability, quality of life |
6.2 When to Refer
| Indication | Referral Pathway |
|---|---|
| Complex insulin regimens | Specialist diabetes team |
| Persistent poor control despite multiple agents | Specialist review |
| Pregnancy or planning pregnancy | Pre-conception counselling; specialist obstetric diabetes service |
| Foot complications | Multidisciplinary foot team |
| Renal impairment progression | Nephrology |
| Cardiovascular events | Cardiology |
7. Pharmacovigilance Considerations
7.1 Adverse Effects of Key Drug Classes
| Drug Class | Common Adverse Effects | Serious Adverse Effects (Requiring Reporting) |
|---|---|---|
| Metformin | GI disturbance (nausea, diarrhoea) | Lactic acidosis (rare; with eGFR <30) |
| Sulfonylureas | Hypoglycemia, weight gain | Severe hypoglycemia |
| Pioglitazone | Weight gain, oedema | Heart failure, bladder cancer risk, fractures |
| DPP-4 Inhibitors | Generally well-tolerated | Pancreatitis (rare); arthralgia |
| SGLT-2 Inhibitors | Genital infections, polyuria | Diabetic ketoacidosis (euglycemic), Fournier’s gangrene (rare), dehydration |
| GLP-1 Agonists | GI disturbance (nausea, vomiting) | Pancreatitis, gallbladder disease |
| Tirzepatide | GI disturbance | Similar to GLP-1 agonists |
7.2 Reporting Adverse Drug Reactions
Healthcare professionals should report suspected adverse reactions to national pharmacovigilance centres. In Egypt, reports can be submitted to:
- Egyptian Drug Authority (EDA)
- Email: pv.followup@edaegypt.gov.eg
- Hotline: 15301
- Website reporting portal
7.3 Signal Detection in Type 2 Diabetes Therapies
Recent pharmacovigilance signals relevant to type 2 diabetes treatment include:
- GLP-1 agonists and gallbladder disease – increased reporting in FAERS and EudraVigilance
- SGLT-2 inhibitors and Fournier’s gangrene – rare but serious; boxed warning in some regions
- DPP-4 inhibitors and arthralgia – class effect requiring patient education
8. Implementation Challenges and Solutions
8.1 Common Barriers to Guideline Implementation
| Barrier | Potential Solution |
|---|---|
| Time constraints in clinical consultations | Use visual summaries (like this NICE guide) to facilitate efficient discussions |
| Patient reluctance to injectable therapies | Discuss benefits gradually; demonstrate devices; address fears |
| Cost restrictions | Prioritize cost-effective options; use least expensive within class when equally suitable |
| Polypharmacy in multimorbidity | Systematic medication review; prioritize agents with multi-organ benefits |
| Health literacy limitations | Use simple language; pictorial aids; involve family/carers |
| Access to specialist services | Virtual consultations; shared care protocols; upskilling primary care |
8.2 Tips for Shared Decision-Making
| Technique | Application |
|---|---|
| Ask about preferences | “What matters most to you about your diabetes treatment?” |
| Use decision aids | Visual tools comparing medication effects on HbA1c, weight, CV risk |
| Check understanding | “Can you tell me in your own words how this medicine works?” |
| Involve family/carers | Include key support people in discussions |
| Document decisions | Record shared decision-making process and patient’s choice |
9. Future Directions
9.1 Emerging Therapies
| Therapy Class | Mechanism | Potential Place in Therapy |
|---|---|---|
| Dual GIP/GLP-1 agonists (tirzepatide) | Dual incretin receptor activation | Superior weight loss and HbA1c reduction; positioning in obesity phenotype |
| Triple agonists (retatrutide) | GIP/GLP-1/glucagon receptor activation | Investigational; potential for greater metabolic benefits |
| Implantable devices | Continuous drug delivery | Improved adherence for injectable therapies |
| Digital therapeutics | Apps, continuous glucose monitoring integration | Personalized treatment adjustments |
9.2 Personalised Medicine Approaches
- Pharmacogenomics: Genetic testing for metformin response (SLC22A1, OCT1 variants); sulfonylurea metabolism (CYP2C9)
- Phenotype-guided therapy: Selecting agents based on predominant patient characteristics (obesity, CVD, renal disease)
- AI-assisted decision support: Algorithms integrating patient data to recommend optimal treatment pathways
10. Conclusions
The 2026 update to NICE guideline NG28 reinforces a patient-centred, evidence-based approach to type 2 diabetes pharmacotherapy. Key messages for healthcare professionals include:
| Principle | Application |
|---|---|
| Shared decision-making is essential | Involve patients in all treatment discussions; respect preferences and values |
| Diet and lifestyle remain foundational | Reinforce healthy living at every opportunity |
| Cardiovascular and renal protection matter | Consider continuing SGLT-2 inhibitors even without full glycaemic response |
| Treatment individualization is key | Match agents to patient characteristics (comorbidities, weight, risk factors) |
| Regular review and optimization | Systematically assess adherence, tolerability, and response before changing therapy |
| Appropriate discontinuation | Stop GLP-1 agonists if underweight or no benefit; avoid GLP-1/DPP-4 combinations |
By implementing these recommendations, healthcare professionals can help adults with type 2 diabetes achieve optimal outcomes—not only in glycemic control but also in cardiovascular health, renal function, weight management, and overall quality of life.
References
- National Institute for Health and Care Excellence. Type 2 diabetes in adults: choosing, reviewing and changing medicines. NICE guideline NG28. Updated 2026. Available from: www.nice.org.uk/guidance/ng28
- International Diabetes Federation. IDF Diabetes Atlas, 10th edition. Brussels: IDF; 2021.
- NICE. Overweight and obesity management. NICE guideline NG246. Available from: www.nice.org.uk/guidance/ng246
- NHS Better Health. Diabetes information. Available from: www.nhs.uk/better-health
- Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis. Lancet. 2019;393(10166):31-39.
- Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(10):776-785.
- American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S158-S178.
- Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the ADA and EASD. Diabetes Care. 2022;45(11):2753-2786.
- U.S. Food and Drug Administration. FDA Adverse Event Reporting System (FAERS) Public Dashboard. Available from: www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard
