Practice Update: Diabetes

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The PCSK9 Inhibitor Alirocumab
Reduces Non-HDL Cholesterol in
Patients with Type 2 Diabetes and
Mixed Dyslipidaemia
The PCSK9 inhibitor alirocumab has been shown to reduce
non-HDL cholesterol in patients with type 2 diabetes and
mixed dyslipidaemia. This outcome of the randomized,
open-label, parallel group ODYSSEY DM – DYSLIPIDEMIA
Study was reported at the American Diabetes Association’s
77th Scientific Sessions, from June 9–13.
Robert R. Henry, MD, of the University of California, Veterans
Administration Medical Center, San Diego, said, “Cardiovas-
cular disease is a significant cause of morbidity and mortality
in patients with type 2 diabetes. Mixed dyslipidemia is present
commonly in these patients and further increases their cardio-
vascular risk.”
Dr Henry and colleagues evaluated alirocumab vs standard care
(either no additional lipid-lowering therapy or ezetimibe, fenofi-
brates, omega-3 fatty acids, or nicotinic acid) in patients with type 2
diabetes and mixed dyslipidemia who were at high cardiovascular
risk (established atherosclerotic cardiovascular disease or at least
one other cardiovascular risk factor) with non-HDL- C inadequately
controlled with the maximum tolerated dosage of statin therapy.
Mixed dyslipidemia was defined as elevations in non-HDL cho-
lesterol and triglyceride levels, often accompanied by low levels
of HDL cholesterol.
The study enrolled 413 patients with type 2 diabetes from 110
centers from the US, Europe, South America, the Middle East,
Australia, and the UK. The trial consisted of a 24-week treatment
period, and a safety follow-up period of 8weeks.
Patients were randomized to either 75 mg of alirocumab (adminis-
tered via an autoinjector every 2 weeks for 24 weeks); or standard
care in a 2:1 ratio. Patients randomized to alirocumab, but who did
not achieve adequate reduction in non-HDL-cholesterol after 12
weeks of follow-up were titrated to 150 mg in a blinded manner.
The primary endpoint was the difference between treatment arms
in percentage change of non-HDL-C from baseline to week 24.
After 24 weeks of treatment, alirocumab reduced the non-HDL-C
significantly, by 32.5% vs usual care. Non-HDL-C is considered
a better predictor of cardiovascular risk than LDL-C levels, par-
ticularly in patients with type 2 diabetes with mixed dyslipidemia.
Additionally, patients who received alirocumab improved in other
lipid parameters vs those who received usual care.
Themajority of patients in the alirocumab group reached the recom-
mended lipid levels with the 75 mg dose. The number of adverse
events was similar between the two treatment arms. Further, aliro-
cumab was well tolerated and did not affect glucose control.
Dr Henry concluded, “The ODYSSEY-DM-DYSLIPIDEMIA Study was
the first trial to compare a PCSK9 inhibitor vs usual care in patients
with type 2 diabetes with lipid disturbances. The results will help cli-
nicians manage mixed dyslipidemia, a persistent clinical challenge
in patients with type 2 diabetes.”
PracticeUpdate Editorial team.
estimated premeal insulin dose. Blood glucose levels were
measured four times daily.
Incorporating glucagon and insulin into automated dosing during
and after exercise reduced exercise-induced hypoglycemia from
6.3 t to 1.0% vs insulin-only usage. The dual-hormone closed-loop
systemwas also more effective than both the predictive low-glu-
cose-suspend dosing system and current-care therapy.
Results across all 4 days from a subset of the 20 adult subjects
from 17 visits showed that time spent in hypoglycemia (<70 mg/
dL) was 1.0% for the dual-hormone system; 3.4% for single-hor-
mone; 1.2% for the predictive low-glucose-suspend system; and
2.1% for current care.
Participants undergoing current care, however, prevented exer-
cise-induced hypoglycemia by keeping their blood sugar levels
significantly higher leading up to the start of exercise. Mean
glucose level after exercise was significantly lower for single-
than with dual-hormone, 67 ± 6 and 100 ± 9 mg/dL, respectively.
Dr Jacobs concluded, “Our findings showed that fully automated
insulin and glucagon delivery, combined with wearable physical
activity sensors that detected exercise, controlled glucose levels
effectively, reduced exercise-induced hypoglycemia, and were
used safely in a home environment. The results suggested that
a dual-hormone closed-loop system with automated detection
of aerobic exercise can be used as a tool to adjust insulin and
glucagon dosing during and after exercise.”
He added, “We plan to explore migrating our system from a
smartphone platform to a smart watch, where exercise can
be detected more easily. These exercise-enabled automated
dosing systems may soon be able to help people with type 1
diabetes exercise safely without fear of hypoglycemia.”
PracticeUpdate Editorial team.
Hybrid closed-loop systems do a great
job improving glucose control overnight,
lowering the risk of hypoglycemia
significantly, and allowing patients and
their families to get a good night’s sleep.
ADA 2017 11
VOL. 1 • NO. 2 • 2017