The great debate: What’s your second-line drug of choice?

Type 2 diabetes

By Kate Marsh

31 Aug 2015

A panel of Australia’s top endocrinologists took to the stage to debate the best second-line treatment options for type 2 diabetes. But was it insulin, GLP-1 analogues, SGLT-2 inhibitors, sulphonylureas, glitazones or DPP-4 inhibitors that won the audience vote?

Professor Steven Colagiuri – Insulin

“Don’t use insulin as a threat”

Director of The Boden Institute and winner of this year’s Kellion Award Professor Steven Colagiuri, opened the session by arguing that insulin should be the first choice after metformin. Only insulin and sulphonylureas had evidence of positive outcomes for reducing microvascular and macrovascular complications and mortality, he told delegates.

Yes there were concerns about hypoglycaemia and weight gain with insulin therapy but in reality weight gain was small and while hypos were increased they were still relatively uncommon, he said. The risk will be even lower with some of the newer insulins, he added.

Rather than using insulin as a threat when all else fails it should be the next step after metformin, he concluded.

Professor Timothy Davis – GLP-1 analogues

“Consider earlier in treatment”

Next to take the stage was Professor Timothy Davis from Fremantle Hospital in Western Australia who debated the benefits of GLP-1 analogues. The aim of treating type 2 diabetes was being able to achieve good glycaemic control, weight loss, avoid hypoglycemia, and minimise other adverse effects. GLP-1 agents ticked all these boxes, he said.

Convenience of administration and treatment satisfaction were also key attributes of the ideal drug, he told delegates, and GLP-1 analogues rated well in these areas.

He encouraged the audience to consider these earlier in treatment, rather than other oral agents that had “questionable benefits”.

Professor Jenny Gunton – SGLT-2 inhibitors

“Patients want glucose to go away”

Next up was Professor Jenny Gunton head of the Centre for Diabetes, Obesity and Endocrinology at the new Westmead Millennium Institute. Patients wanted glucose to go away and this was exactly how SGLT-2 inhibitors worked, she told delegates.

Patients also wanted to lose weight and SGLT-2 inhibitors helped with this. They also don’t want to take lots of pills or injections and these agents were taken only once per day, she pointed out. Their blood pressure lowering effect may also reduce the need for anti-hypertensive treatment, she added.

Associate Professor Richard O’Brien – Sulphonylureas

“They don’t deserve the bad press”

A/Prof Richard O’Brien Director of the Lipid Service at the Austin Hospital spoke of the efficacy of sulphonylureas in achieving glycaemic targets and their evidence for reducing CVD risk.

He then went on to argue against what he referred to as ‘bad press’ around sulphonylureas. These agents don’t exhaust the beta-cells, he told delegates, citing evidence that progression of diabetes occured regardless of treatment.

Hypoglycemia was a risk but this risk varied between different agents, with gliclazide showing a low risk and glimenclamide carrying a much higher risk. After lifestyle modification and then metformin, sulphonylureas should be the next step but it’s important to choose the right agent – i.e. one with a lower risk of hypoglycemia, he concluded.

Dr Trisha O’Moore Sullivan – Glitazones

“At least we know what we know”

Dr Trisha O’Moore-Sullivan, Director of the new Mater Young Adult Health Centre in Brisbane conceded she had been given the most difficult task – convincing the audience of the benefits of glitazones.

She went on to highlight the efficacy and durability of these agents, showing that when added to metformin they are more potent than many of the other choices.

She also highlighted data from the ADOPT study, showing that as monotherapy glitazones were better than other agents for reducing progression of type 2 diabetes. Agreeing that there are some risks – mainly increase risk of heart failure and bone fracture, she showed evidence that MI risk was not increased and stroke risk may be reduced. The risks of bladder cancer with pioglitazone appeared small and possibly only a concern in those at higher risk.

Glitazones have known, manageable side effects, she concluded. “At least we know what we know and we know what we don’t know, while with other agents there are a whole lot of unknowns that we don’t yet know” she told delegates.

Professor Jonathan Shaw – DPP-4 inhibitors

“The Rolls Royce of the car world”

The final speaker to the stage was A/Prof Jonathan Shaw from Melbourne’s Baker IDI Heart and Diabetes Institute. He described the other speakers as being like used car salesman – trying to sell drugs with a variety of downsides (including weight gain, risk of hypoglycemia, GI side effects, increased fracture risk and other complications).

DPP-4 inhibitors are more like the Rolls Royce of the car world, he told delegates. He presented studies looking at patient preferences for oral hypoglycaemic agents showing that their key concerns include cost, efficacy, hypo risk, weight gain, GI side effects and other complications.

DPP-4 inhibitors tick all the boxes, having a similar HbA1c lowering effect to other agents, an excellent safety profile, and simple administration, he said. “If a drug aligns well with patient preferences for the ideal drug, they are more likely to take it”, he told delegates.

What the audience thought.

According to the audience sulphonylureas took first place, with 35% of delegates voting these as their drug of choice after metformin. However Chair of the session Professor Sophia Zoungas, Chair of Diabetes, Vascular Health and Ageing at Monash University said: “We have a wide range of agents to choose from and any of these choices are valid, depending on the patient”.

There was agreement from the panel and the floor that individualised treatment was important and that no one size fits all and there was a need to discuss the options with patients, including the benefits and risks.

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