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SA JOURNAL OF DIABETES & VASCULAR DISEASE Saxagliptin (Onglyza) launched in South Africa The DPP-4 inhibitor saxagliptin was cations, presented in 1999 at the EASD in and other agents, and with no significant Barcelona. In the UKPDS, metformin therapy weight gain. ‘Treatment with saxagliptin cal meetings in South Africa, arranged by was the only winner, and after UKPDS, we when extrapolated over the long term does Astra Zeneca and Bristol Myers Squibb. This thought that we should reach for lower much better than the sulphonylureas’, Dr incretin-enhancing agent is recommended HbA levels to obtain macrovascular ben- for early use with lifestyle therapy in type efits’, he said.
‘The evaluation of cardiovascular safety More than 25 000 patients participated with saxagliptin8 is very reassuring as there is formin and other anti-diabetic agents, to in the ACCORD, VADT and ADVANCE no evidence that it increases cardiovascular help regain glucose control.
studies,3-5 in which near-normal glycaemic risk when used as monotherapy or in com- Dr Wayne May, endocrinologist and CDE control should be achieved, targeting HbA bination with other agents. In fact, a long- practitioner based in Cape Town pointed levels of lower than 6.5 to 7%. However, term outcome study is currently underway, out that clinicians need to tell their patients ACCORD needed to be stopped early due to the SAVOR-TIMI 53 trial, which is 18 months that diabetes is a chronic condition which an increased mortality of 22% in the inten- into execution and the results should be progresses over time and that current treat- available in 2015’, Dr Jacob pointed out.
ment cannot halt this progression. Lifestyle One important side effect of intensified Patients who will benefit most from modification is the cornerstone of therapy, therapy was seen more frequently: weight saxagliptin use are newly diagnosed patients but as lifestyle efforts (weight loss, exercise) gain and hypoglycaemia. This was a sur- diminish, the need for more complex regi- prise, as when these trials were planned, with lifestyle changes. Also, all patients who the importance of hypoglycaemic events should never have a hypoglycaemic event ‘What patients fear at this juncture is was not considered to be so relevant.
are ideal candidates for saxagliptin, such as ‘In fact, the analysis following the VADT truck and regular motor car drivers, elderly study of the factors most predictive of future patients and those who have already had a mia is experienced as feelings of extreme cardiovascular death showed that the occur- confusion, anxiety, irritability and sweaty rence of a severe hypoglyacaemic event discomfort. Hypoglycaemia also reduces was a better predictor of mortality than a Julia Aalbersa patient’s satisfaction with their diabetes prior myocardial infarction or other vascular therapy and interferes with overall compli- event’, Dr Jacob stressed. In the ADVANCE 1. UKPDS. Intensive blood glucose control with sulphonylureas or insulin compared with conventional study, severe hypoglycaemia was also asso- treatment and risk of complications in patients with Weight gain is also a major concern for ciated with a greater risk of both micro- and type 2 diabetes (UKPDS 33) UK Prospective Diabetes patients. Although metformin as first-level macrovascular events.
Study. Lancet 1998; 352(9131): 837–853.
treatment for type 2 diabetes does not cause ‘In addition, in the older patient (mean 2. Viberti G, Kahn SE, Greene DA, et al. A diabetes weight gain, most subsequent therapies do. age 65 years), it has been shown that risk outcome progression trial (ADOPT) Diabetes Care
2002; 25(10): 1737–1743.
In the UKPDS study series, patients gained of dementia was correlated with episodes of 3. Punthakee Z, Miller ME, Launer LJ, et al. Poor up to 8 kg in 12 years, while in the ADOPT hypoglycaemia. The greater attributable risk cognitive function and risk of severe hypoglycaemia trial, average weight gain was 4.8 kg in five of dementia was 2.39% per year in individ- in type 2 diabetes – post hoc epidemiologic analysis uals with a history of hypoglycaemia, com- of the ACCORD trial. Diabetes Care 2012 Feb 28.
‘Sulphonylureas and insulin are the pared to those without hypoglycaemia’.
4. VADT investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N worst offenders with regard to weight gain’, Engl J Med 2009; 360(2): 129–39.
Dr May noted. ‘In order to reduce overall car- treatment and follow the physiological route 5. Van Dieren S, Szemichow S, Chalmers J. Weight diovascular risk, we also need to hit out on all of better glucose control without hypogly- changes and their predictors amongst 11 1104 fronts: lowering cholesterol and blood pres- patients with type 2 diabetes in the ADVANCE trial. Diabetes Obes Metab 2012 Jan 9. Doi 10.111/j sure, and keeping glucose levels to target.’ reactive approach of intensifying therapy Supporting this approach, Dr Stephan only when the HbA level deteriorates’, Dr 6. Whitmer RA, Karter AJ, et al. Hypoglycaemic Jacob from the Institute for Cardio- Jacobs recommended.
episodes and risk of dementia in older patients with Metabolic Prevention and Therapy, University ‘Referring to the newer agents, the best type 2 diabetes mellitus. J Am Med Assoc 2009; of Tubingen, Germany, noted that lowering agent to add to metformin is either a DPP-4 301(15): 1562–1572.
7. Goke B, Gallwitz B, Eriksson J, et al. Saxagliptin blood pressure and cholesterol levels reduces inhibitor or a GLP-1 agonist, which do not is non-inferior to glipizide in patients with type the risk of cardivascular events to a greater adversely affect cardio-metabolic risk by 2 diabetes mellitus inadequately controlled on enhancing weight gain or inducing hypogly- metformin alone – a 52-week randomised controlled ‘In my view, this is because, in the diabe- caemic episodes’, Dr Jacob pointed out.
trial. Int J Clin Prac 2010; 64(12): 1619–1631.
tes world, we set out primarily to beat HbA , 8. Cobble ME, Frederich R, et al. Saxagliptin for the treatment of type 2 diabetes mellitus: assessing particularly after the disappointing results of have a very low rate of hypoglycaemia, cardiovascular data. Cardiovasc Diabetol 2012; 16:
similar to placebo, when added to metformin

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