GP Connect Clinical Feature by Dr Karen M Rothacker MBBS FRACP, Endocrinologist at Royal Perth Hospital and the Keogh Institute
New pharmacological therapies to manage type 2 diabetes continue to emerge. The choice of available therapies allows individualised treatment thus offering the possibility for safer, more effective and holistic patient management.
Prior to initiating or intensifying pharmacological therapy for a person with type 2 diabetes it is important to:
- Be confident in the diagnosis of type 2 versus an alternative form of diabetes (e.g. type 1 diabetes, pancreatic diabetes)
- Know the individual’s co-morbid health conditions
- Determine their individual glycaemic target
- Consider whether non-pharmacological interventions could help them achieve their glycaemic target.
Clinical features raising the possibility of non-type 2 diabetes include alean build or unintentional weight loss, autoimmunity or recurrent pancreatitis. More acute onset osmotic symptoms may also be a clue. If a finger-prick glucose is >15 mmol/L, ketones should be measured. If a patient is hyperglycaemic (or normoglycaemic on sodium glucose co transporter 2 (SGLT2) inhibitor therapy), with ketones >1.5 mmol/L on finger-prick or 3+ on urine dipstick, urgent specialist diabetes assessment/Emergency Department review is warranted.
If ketones are absent but suspicion for non-type 2 diabetes remains, measurement of c-peptide, IA-2 and GAD-65 antibodies would be useful prior to specialist referral.
Knowing a patient’s co-morbid health conditions helps determine their individual glycaemic target as well as the preferred pharmacological therapy. While an HbA1c ≤7% (53 mmol/mol) is a general target, in patients managed with lifestyle modification and/or metformin or younger patients without co-morbidities a tighter target HbA1c of ≤6.0 – 6.5% (42 – 48 mmol/mol) may be appropriate. By contrast, a more relaxed glycaemic target is suggested in patients who are older, have significant co-morbidities or a limited life expectancy.
Non-pharmacological interventions which may improve glycaemic control include:
- Dietary modification
- Increasing physical activity/breaking up sedentary time
- Psychosocial approaches to improve motivation and adherence with diabetes management (e.g. psychological support, medication aids)
- In those patients on insulin, reviewing injection technique
Considering the above, referral to a diabetes educator, dietitian, exercise physiologist or community program may be appropriate. In patients with type 2 diabetes who are overweight or obese, intensive weight management (potentially using very low-calorie meal replacement products, weight loss pharmaceuticals or bariatric surgery) can significantly improve glycaemic control.
When prescribing pharmacological therapy in type 2 diabetes, metformin is generally considered first line. Individualised add-on therapy considers:
- Patient’s co-morbidities, especially history of atherosclerotic cardiovascular disease, heart failure and chronic kidney disease
- Desire for weight loss
- Preference to avoid hypoglycaemia
- Acuity of need to improve hyperglycaemia.
Details regarding the classes, agents, properties, and PBS considerations of the glucose lowering therapies are available on the Australian Type 2 Diabetes Management Algorithm
If a patient has established atherosclerotic cardiovascular disease, a SGLT2 inhibitor or GLP-1 receptor agonist would be the favoured second line agent as studies have shown cardiovascular benefit. A SGLT2 inhibitor would be preferred over GLP-1 agonist in the setting of heart failure.
In the setting of chronic kidney disease (but eGFR ≥45 ml/min/1.73m2), SGLT2 inhibitors reduce chronic kidney disease progression. SGLT2 inhibitors and GLP-1 agonists are associated with weight loss whilst not causing hypoglycaemia. SGLT2 inhibitors carry a risk for ketoacidosis and should be discontinued in the event of fasting or intercurrent illness. SGLT2 inhibitor and GLP-1 agonists are safe to use concurrently but are not presently supported in combination under the Pharmaceutical Benefits Scheme.
Sulfonylureas and dipeptidyl peptidase (DPP-4) inhibitors may also be used as second line add-on agents or as triple or quadruple oral therapy. Sulfonylureas carry a risk of hypoglycaemia and may cause modest weight gain. DPP-4 inhibitors are considered weight neutral.
Where more rapid improvement in moderate to severe hyperglycaemia is required (e.g. intercurrent infection or high dose steroid therapy), insulin is likely the most appropriate treatment given its prompt onset of action and ability to quickly titrate dose according to changing patient circumstance. Insulin therapy may also be initiated at diagnosis of type 2 diabetes where there are moderate to severe osmotic symptoms. With lifestyle changes and initiation of other glucose lowering therapy insulin can possibly be subsequently discontinued. Insulin treatment may ultimately be required in patients with longer standing type 2 diabetes given the natural history of progressive beta cell failure.
See also “Glycaemic Control for Type 2 Diabetes” HealthPathway.