PracticeUpdate: Endocrinology

EASD 2016

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Platelets frompoorly controlled type 2 diabetic patients lost not only their ability to protect against ischaemia/reperfusion injury but also induced an increase of infarct size and lactate dehydrogenase release, amarker of necrosis. >9

The analysis demonstrated the difficulty of maintaining haemoglobin A1c to goal over 3 years, even in a clinical trial setting. >6

The findings support the concept that (micro)vascular structural brain damage precedes the clinical diagnosis of type 2 diabetes andmay contribute to the cerebral complications of prediabetes and type 2 diabetes. >8

Pregnancy outcomes of women with gestational diabetes are worse but most differences are due to higher body weight

Though the pregnancy outcomes of women with World Health Organization (WHO) classified gestational diabetes have been shown to be worse than those with normal glucose tolerance, most of the differences were explained by the higher body weight of these women, finds a retrospective database analysis.

mellitus, even after taking into account the weight difference between women with NICE-classified gestational diabetes mellitus and those with normal glucose tolerance. These outcomes support use of the less strin- gent cutoff values recommended by NICE. The data suggests that treatment focused on weight gain during pregnancy might be enough the improve outcomes of these ‘mild’ gestational diabetes cases (WHO-classified gestational diabetes mellitus). Dr Tabak said, “The finding that the moth- er’s weight explains some of the differences in outcomes is hardly surprising. The real prob- lem is to find the right cutoff, where the role of maternal weight becomes less important than that of glycaemia. Our study offers some direction to this problem, but the final answers should come from randomised trials.”

A.G. Tabak, MD, of University College London, UK, and Semmelweis University, Budapest, Hungary, explained that the WHO issued new recommendations for the diagnosis of gestational diabetes mellitus in 2013. The new diagnostic criteria approximately double the prevalence of gestational diabetes versus the previous WHO recommendation. Several professional bodies (including the National Institute for Health and Care Excellence [NICE]) recommended less stringent cutoff values to limit the prevalence of gestational diabetes. Given that the diagnosis of gestational diabetes has been based on the WHO-1999 criteria in the last decade in Hungary, a large proportion of women currently considered to have gestational diabetes remained untreated. Dr Tabak said, “The WHO 2013 diagnostic recommendation of gestational diabetes is based on observational findings of the multinational Hyperglycemia and Adverse Pregnancy Out- comes (HAPO) study. These recommendations lack the support of randomised clinical trials.” He added, “We tried to fill this evidence gap by providing retrospective analytic data on the outcomes of the mildest forms of gestational diabetes.” Dr Tabak and colleagues set out to compare pregnancy outcomes of women with untreated gestational diabetes (according to WHO 2013, WHO–Gestational Diabetes Mellitus and

NICE 2015, and NICE–Gestational Diabe- tes Mellitus) and women with normal glucose tolerance. During a universal screening program in western Hungary, 4828 pregnant women had a 75 g oral glucose tolerance test using three- point glucose determinations in 4 years. Based on these oral glucose tolerance tests, 696 (14.4%) WHO–Gestational Diabetes Mellitus and 478 (9.9%) NICE–Gestational Diabetes Mellitus cases were diagnosed retrospectively. A total of 251 women who were treated for gestational diabetes were excluded from the analysis. Untreated women with gestational diabetes were older and had higher fasting 60-minute, and 120-minute blood glucose, and blood pressure. No difference in marital status or education was found. Women with ges- tational diabetes had higher body weight, though weight gain was similar in all groups (13 kg). WHO–Gestational Diabetes Mellitus newborns had a higher birthweight (144 ± 31 g), Newborns of women who had NICE– Gestational Diabetes Mellitus were of similar birthweight (66 ± 43 g) to controls. Several important outcomes were more frequent in groups classified as having ges- tational diabetes by either criterion including hypertension during pregnancy (see box). No difference in the risk of preeclampsia and malformations was found. After adjustment

for the mothers’ weight at delivery, women with WHO-classified gestational diabetes mellitus had similar outcomes as women with normal glucose tolerance. While for the group with NICE-classified gestational diabetes mellitus, induced delivery and acute caesarean section remained more frequent. Dr Tabak concluded that, though the preg- nancy outcomes of women with WHO-classi- fied gestational diabetes mellitus were worse than those of women with normal glucose toler- ance, most of the differences were explained by the higher body weight of these women. Some outcomes remained worse for women with NICE-classified gestational diabetes

Outcomes that were more frequent in groups classified as having gestational diabetes by either the WHO or NICE criteria. • WHO–Gestational Diabetes Mellitus, odds ratio 1.56, 95% CI 1.03–2.38 • NICE–Gestational Diabetes Mellitus 1.58, 95% CI 0.90–2.78 Induced delivery: • WHO–Gestational Diabetes Mellitus, odds ratio 1.25, 95% CI 0.98–1.60 • NICE–Gestational Diabetes Mellitus 1.54, 95% CI 1.11–2.13 Forceps or vacuum use: • WHO–Gestational Diabetes Mellitus, odds ratio 1.29, 95% CI 1.01–1.64 • NICE–Gestational Diabetes Mellitus 1.35, 95% CI 0.97–1.87 Acute caesarean section: • WHO–Gestational Diabetes Mellitus, odds ratio 1.25, 95% CI 0.98–1.60 • NICE–Gestational Diabetes Mellitus 1.54, 95% CI 1.11–2.13 Macrosomia >4000 g: • WHO–Gestational Diabetes Mellitus, odds ratio 1.95, 95%CI 1.39–2.72 • NICE–Gestational Diabetes Mellitus 1.16, 95% CI 0.67–2.00

Patients who switch from sitagliptin to liraglutide experience better glycaemic control, weight loss, and reduced SBP and hypoglycaemic episodes By switching from sitagliptin liraglutide, patients insufficiently controlled on sitagliptin and metformin are more likely to improve in glycaemic control, lose weight, and reduce their systolic blood pressure and hypoglycaemia. T his conclusion, based on results of the randomised, parallel-group, double-blind, composite endpoints at week 26 were: • HaemoglobinA <7.0% (53 mmol/ mol) with no weight gain achieved each of the four composite end- points by switching

not achieving adequate glycaemic control with sitagliptin + metformin. Dr Bailey and colleagues com- pared the proportion of subjects meeting four composite endpoints at 26 weeks, relating to glycaemia, body weight, systolic blood pressure, and hypoglycaemia outcomes. Eligible subjects were at least 18 years of age, had haemoglobin A 7.5–9.5% (58–80 mmol/mol), body mass index ≥ 20 kg/m 2 , had been treated with stable doses of sitagliptin (100 mg daily) and met- formin ( ≥ 1500 mg daily or maximum tolerated dose ≥ 1000 mg daily) for ≥ 90 days, and were randomised 1:1 to switch to liraglutide 1.8 mg or continue sitagliptin 100 mg once daily, both + metformin. Predefined

Courtesy of EASD 2016

weight gain and no confirmed hy- poglycaemic episodes: 48.3% vs 24.2%, odds ratio 3.40, 95% CI 2.11; 5.49, P < 0.0001. Dr Bailey concluded that switch- ing from sitagliptin to liraglutide resulted in more subjects achieving each of the composite endpoints analysed, than those who continued sitagliptin. By switching from sitag- liptin to liraglutide, patients insuf- ficiently controlled on sitagliptin and metformin are more likely to meet clinically relevant goals relating to glycaemia, body weight, systolic blood pressure, and hypoglycaemia.

double-dummy, active-controlled LIRA-SWITCH trial, was presented at the meeting. T. S. Bailey, MD, of the AMCR Institute, Escondido, California, explained that limited clinical evidence is available to guide treat- ment choices beyond the addition of another drug to achieve glycaemic target when second-line therapy is inadequate for patients with type 2 diabetes. The LIRA-SWITCH trial com- pared the efficacy and safety of switching from sitagliptin to lira- glutide as an add-on to metformin in subjects with type 2 diabetes

from sitagliptin to liraglutide than those who continued sitagliptin: • Haemoglobin A <7.0% with no weight gain: 48.3% vs 24.2% (lira- glutide and sitagliptin, respectively), odds ratio 3.40, 95%CI 2.11; 5.49, P < 0.0001 • Haemoglobin A<7.0%, with no weight gain and systolic blood pressure <140 mmHg: 44.9% vs 19.2%, odds ratio 3.88, 95% CI 2.36; 6.39, P < 0.0001 • Haemoglobin A reduction ≥ 1.0% with no weight gain: 52.8% vs 29.1%, odds ratio 2.85, 95% CI 1.82; 4.47, P < 0.0001 • Haemoglobin A<7.0%, with no

• Haemoglobin A <7.0%, with no weight gain and systolic blood pressure <140 mmHg • Haemoglobin A reduction ≥ 1.0% with no weighwt gain. In addition, a post hoc analysis of haemoglobin A<7.0%, with no weight gain and no confirmed hypo- glycaemic episodes was conducted. A total of 407 subjects (male 60%, mean age 56 years, body mass index 32 kg/m 2 , haemoglobinA 8.3% [67 mmol/mol], type 2 diabetes dura- tion 8 years) were randomised (lira- glutide, n = 203; sitagliptin, n = 204). At week 26, more subjects

VOL. 1 • No. 3 • 2016