Pathways – Dr Duncan Fowler Ipswich Hospital Diabetes Centre will have a more active role in supporting primary care pathways, through education, its advice line and email, outreach and face-to-face contact where appropriate Pathways are usually out of date and can’t cover all eventualities Care should be individualised and the integrated service will provide ongoing advice based on up to date data and medications Having said that: pathways still have a role

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care 2012;35:1364–1379 Diabetologia 2012;55:1577–1596

Fig. 2. T2DM Antihyperglycemic Therapy: General Recommendations Moving from the top to the bottom of the figure, potential sequences of anti-hyperglycaemic therapy. In most patients, begin with lifestyle changes; metformin monotherapy is added at, or soon after, diagnosis (unless there are explicit contraindications). Fig. 2. T2DM Antihyperglycemic Therapy: General Recommendations

Fig. 2. T2DM Antihyperglycemic Therapy: General Recommendations If the A1c target is not achieved after ~3 months, consider one of the 5 treatment options combined with metformin (dual combination): a sulfonylurea, TZD, DPP-4 inhibitor, GLP-1 receptor agonist or basal insulin. Note that the order in the chart is determined by historical introduction andr oute of administration and is not meant to denote any specific preference. Choice is based on patient and drug characteristics, with the over-riding goal of improving glycemic control while minimizing side effects. Shared decision-making with the patient may help in the selection of therapeutic options. Rapid-acting secretagogues (meglitinides) may be used in place of sulfonylureas. Consider in patients with irregular meal schedules or who develop late postprandialhypoglycemia on sulfonylureas. Other drugs not shown (α-glucosidase inhibitors, colesevelam, dopamine agonists, pramlintide) may be used where available in selected patients but have modest efficacy and/or limiting side effects. In patients intolerant of, or with contraindications for, metformin, select initial drug from other classes depicted, and proceed accordingly. Consider starting with 2-drug combinations in patients with very high HbA1c (e.g. ≥9%). Fig. 2. T2DM Antihyperglycemic Therapy: General Recommendations

Fig. 2. T2DM Antihyperglycemic Therapy: General Recommendations Further progression to 3-drug combinations are reasonable if 2-drug combinations do not achieve target. If metformin contraindicated or not tolerated, while published trials are generally lacking, it is reasonable to consider 3-drug combinations other than metformin. Insulin is likely to be more effective than most other agents as a third-line therapy, especially when HbA1c is very high (e.g. ≥9.0%). The therapeutic regimen should include some basal insulin before moving to more complex insulin strategies (see Fig. 3) Fig. 2. T2DM Antihyperglycemic Therapy: General Recommendations

Ultimately, more intensive insulin regimens may be required (see Figure 3.) Dashed arrow line on the left-hand side of the figure denotes the option of a more rapid progression from a 2-drug combination directly to multiple daily insulin doses, in those patients with severe hyperglycaemia (e.g. HbA1c ≥10.0-12.0%). Consider beginning with insulin if patient presents with severe hyperglycemia (≥300-350 mg/dl [≥16.7-19.4 mmol/l]; HbA1c ≥10.0-12.0%) with or without catabolic features (weight loss, ketosis, etc).

Fig. 3. Sequential Insulin Strategies in T2DM Basal insulin alone is usually the optimal initial regimen, beginning at 0.1-0.2 U/kg body weight, depending on the degree of hyperglycemia. It is usually prescribed in conjunction with 1-2 non-insulin agents. In patients willing to take >1 injection and who have higher A1c levels (≥9.0%), BID pre-mixed insulin or a more advanced basal plus mealtime insulin regimen could also be considered (curved dashed arrow lines). When basal insulin has been titrated to an acceptable FPG but A1c remains above target, consider proceeding to basal + meal-time insulin, consisting of 1-3 injections of rapid-acting analogues. A less studied alternative—progression from basal insulin to a twice daily pre-mixed insulin—could be also considered (straight dashed arrow line); if this is unsuccessful, move to basal + mealtime insulin. The figure describes the number of injections required at each stage, together with the relative complexity and flexibility. Once a strategy is initiated, titration of the insulin dose is important, with dose adjustments made based on the prevailing BG levels as reported by the patient. Non-insulin agents may be continued, although insulin secretagogues (sulfonylureas, meglitinides) are typically stopped once more complex regimens beyond basal insulin are utilized. Comprehensive education regarding self-monitoring of BG, diet, exercise, and the avoidance of, and response to, hypoglycemia are critical in any patient on insulin therapy. Fig. 3. Sequential Insulin Strategies in T2DM Diabetes Care 2012;35:1364–1379 Diabetologia 2012;55:1577–1596

Indications and therapeutic options for dual therapy in patients with Type 2 diabetes

Commonly occurring situations Intermittent illnesses: Stop metformin Rehydrate with non-sugary drinks Hypercholesterolaemia: Atorvastatin – escalate up to 80mg, then refer for consideration of ezetimib Erectile dysfunction: Diabetes is a risk factor for erectile dysfunction but assessment and management of patients is similar Medical, psychiatric, surgical, relationship, sexual and drug history Clinical examination, including genital examination, blood pressure, heart rate and waist circumference Serum lipids, fasting plasma glucose, recent HbA1c, morning testosterone and SHBG Consider digital rectal examination and PSA Combined oral contraceptive: Diabetes poses no additional independent risk factor to venous thromboembolism to the established risk factors

Other Pathways Renal Impairment Hypoglycaemia Anti-platelet therapy – noting that NICE Clinical Guidelines have been superceded by some more recent evidence GLP-1 agonists SGLT2 inhibitors Foot protection Autonomic neuropathy, explosive nocturnal diarrhoea and neuropathic pain