Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

Gemigliptin is a potent, selective, and long-acting DPP-4

inhibitor and also effective and well tolerated in patients

with type 2 diabetes mellitus (T2DM) as either inmonotherapy

or in combination therapy. In addition, it is more effective in

reducing glycemic variability than sitagliptin or SU as initial

combination therapy with metformin in drug-naïve patients

with T2DM. Various studies have shown that gemigliptin is

optimized with having potent efficacy, reliable safety and

compliance benefits for T2DM. In this talk, I will review the key

characteristics of gemigliptin and discuss its potential benefits

in the treatment of type 2 diabetes.

Lunch Seminar

–

Servier

LN04-1

Update on existing therapy

–

with a focus on SUs

Richard O

’

BRIEN

University of Melbourne, Australia

Metformin is recommended, in most guidelines, as first line

treatment for overweight patients with type 2 diabetes.

Sulphonylureas (SU) remain an initial option for non-obese

patients and are useful second line therapy because they are

effective and well tolerated. However, there is a common

misconception that SU are inferior to modern agents such

as DPP4 inhibitors in terms of complications prevention,

cardiovascular (CV) risk and durability of control. Apart from

metformin, SU are the only oral diabetes therapies to have

shown clear reductions inmicrovascular complications in long

term end-point trials. SGLT 2 inhibitors show promise with a

recent study suggesting CV protection, but further studies are

awaited. Also, these agents are not effective in patients with

reduced renal function and are expensive. The effect of

intensive glycaemic control with gliclazide (Diamicron MR

)

was studied in the ADVANCE trial. 11,140 subjects were

randomised to intensive therapy aiming for an HbA1C of

<6.5%, or standard care, for 5 years. The intensive group

attained an HbA1C of 6.4% vs. 7.0% in the control group.

Intensive control reducedmicrovascular endpoints by 14% and

had no adverse effect CV endpoints. These results were

consistent with the effects of SU therapy seen in a previous

end-point trial, the UKPDS. In that study, an HbA1C reduction

of 1% resulted in a 25% reduction in microvascular endpoints

over a 10 year follow up period. Gliclazide has been shown to

cause less hypoglycaemia than comparable SU

’

s, and it is

interesting to note that the rate of hypoglycaemia in ADVANCE

was much lower than that of comparable studies.

In the ADVANCE-ON study, 84% of the ADVANCE cohort

(8,494 people) were followed for a further 5.4 years after the

original trial finished. The difference in HbA1C between the

intensive and control groups disappeared by the first post-trial

visit, and remained similar at the end of ADVANCE-ON

(intensive 7.2%, control 7.4%). End-stage renal disease result-

ing in death or dialysis was reduced by 64% (p = 0.007),

suggesting a persisting microvascular benefit from earlier

intensive glucose control with a gliclazide MR based regimen.

Diabetes is a progressive process and

cell function declines

gradually over time. In the UKPDS,

cell function declined at a

similar rate in SU, metformin and insulin treated patients.

Interest has focused on the possibility that newer diabetes

drugs might preserve

cell function. The ADOPT study com-

pared the effects of metformin, glyburide and rosiglitazone on

glycaemic control over 5 years. Although rosiglitazone initially

appeared to delay the progression of diabetes, by 5 years the

decline in

cell functionwas similar in all 3 groups. Only short-

term data exists for the DPP4 inhibitors, but studies to date

suggest durability of control is very similar to SU

’

There have, over many years, been concerns about the effect

of SU

’

s on the risk of cardiovascular complications. One

possible mechanism is that many of these drugs prevent the

opening of myocardial K

-ATP channels, thereby increasing

the effects of ischemia on the myocardium. Gliclazide does

not have this effect and, in the ADVANCE and ADVANCE-ON

trials, there was no adverse effect on cardiovascular end-

points. Also, gliclazide appears to have some unique proper-

ties not shared by other SU

’

s. We have found that gliclazide,

but not other SU

’

s or metformin, inhibited the oxidation of

LDL and reduced markers of oxidative stress in diabetic

patients. In another study, both metformin and gliclazide

but not glibenclamide inhibited the progression of the intima-

media thickness of the carotid artery, an index of the

progression of atherosclerosis.

’

s, and particularly gliclazide (Diamicron MR

) are effective

and well tolerated agents for the treatment of type 2 diabetes

and their use is well validated by large scale end-point studies.

’

s differ in their propensity to cause hypoglycaemia and in

their vascular effects, and this should be taken into account

when prescribing. Sulphonylureas are likely to retain a major

role in diabetes treatment algorithms for the foreseeable

future.

Lunch Seminar

–

Boehringer-Ingelheim

LN09-1

New horizons for managing type 2 diabetes

Hung-Yuan LI

Department of Internal Medicine, National Taiwan

University Hospital, Taipei, Taiwan

Type 2 Diabetes Mellitus (T2DM) is a complex cardio-metabolic

disorder characterized by insulin resistance, pancreatic beta

cell dysfunction and hyperglycaemia. Due to the progressive

nature of T2DM, maintaining glycemia as close to normal as

possible can significantly reduce microvascular complica-

tions. Long-term reduction in macrovascular disease was

also observed, if the glycemic control was implemented soon

after diagnosis. Current treatment guidelines emphasize the

importance of individualizing patient care with regard to both

goals and therapies. A number of different diabetes therapies

exist, allowing for personalized therapy regimens. Engage

patients by involving them in healthcare decisions and

selecting therapies that fit with their needs and preferences,

which may enhance adherence to therapy. As the disease

progresses, changes in

-cell function and insulin resistance

can limit the ability of certain oral antidiabetic agents to

reduce blood glucose levels.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new

class of antidiabetic agents through insulin independent

pathway that reduce hyperglycemia in patients with T2DM

by reducing renal glucose reabsorption and thus increasing

urinary glucose excretion (UGE). Most recent guidelines have

already included SGLT2 inhibitors as one of the dual or triple

therapy options, even concomitantly treatment with insulin.

Drugs within the class of SGLT2 inhibitors have shown various

clinical, mechanistic and theoretical effects on cardiovascular

pathways and some of the cardiovascular outcome studies

have been conducted to assess whether any of the individual

SGLT2 inhibitor compounds has an impact on cardiovascular

outcomes.

Based on the placebo-controlled phase III trials in T2DM

patients taking empagliflozin (one of the SGLT2 inhibitors),

improved hemoglobin A1c (HbA1c) has been noted in mono-

therapy or add-on therapy with a low risk of hypoglycemia,

reduced body weight and blood pressure, without increases in

heart rate. Further investigations have also revealed the

efficacy and safety data of empagliflozin in patients with

certain range of impaired renal functions. In addition,

empagliflozin has also been reported to reduce other CV risk

markers such as visceral fat mass, uric acid, arterial stiffness

and glomerular hypertension. With the positive results

Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1

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