doi: 10.1111/1753-0407.

12644 Journal of Diabetes 10 (2018), 353–356

International Diabetes weight reduction (P < 0.0001 for Ann M. Carracher, Payal
Federation 2017 comparison). Dr Lean announced H. Marathe, and Kelly L. Close
that economic analyses are underway are of Close Concerns (http://
More than 8000 delegates from
to determine the cost-effectiveness of www.closeconcerns.com), a
165 countries gathered in Abu Dhabi,
delivering the intensive weight loss healthcare information
United Arab Emirates, for the Inter-
intervention (in DiRECT, the treat- company focused exclusively
national Diabetes Federation’s 2017
ment was implemented by modestly on diabetes and obesity care.
Congress. Dr Mike Lean (University
trained usual care providers). He Close Concerns publishes
of Glasgow, Glasgow, UK) presented
shared that 32 participants dropped Closer Look, a periodical that
1-year data from the DiRECT trial,1
out of the treatment arm due to the brings together news and
which randomized 298 participants
intervention’s demands or lack of insights in these areas. Each
(recently diagnosed adults with type
appeal. Dr Roy Taylor (Newcastle month, the Journal of Diabetes
2 diabetes (T2D; not on insulin) to
University, Newcastle, UK) shared in includes this News feature, in
intensive weight loss intervention
discussion that shorter duration of which Carracher, Marathe, and
(withdrawal of antidiabetic or antihy- diabetes predicted responders versus Close review the latest
pertensive drugs, total diet replace- non-responders in a subgroup of developments relevant to
ment with approximately DiRECT, and Dr Lean later clarified researchers and clinicians.
800 calories/day for 3–5 months, that people with longer duration of
stepped food reintroduction for diabetes who lose a substantial
2–8 weeks, and structured support for amount of body weight can achieve
long-term weight maintenance) or to diabetes remission, although the best
standard of care for the UK. Dr Lean results appear in individuals with
reported that 24% of participants shorter disease duration; 2- and 3-year
receiving intensive weight loss inter- data from DiRECT are still being
vention (36/149) achieved ≥15 kg collected.
(~33 lb) weight loss, and that 46% of During the same symposium,
this treatment arm (68 individuals) researchers presented findings from
achieved diabetes remission. Mean the DISCOVER study,2 a large-scale
weight loss for the intervention group effort in real-world data collection
was 14.5 kg (~30 lb) after meal spanning 38 countries and enrolling
replacement, and mean weight regain 15 992 patients with T2D, about to
at 12 months was 2 kg (~4.4 lb). In initiate second-line therapy. The pri-
those losing ≥15 kg, 86% achieved mary objective of the program, as
diabetes remission, and Dr Lean thus presented by Dr Linong Ji (Peking
underscored the apparent relationship University Diabetes Center, Beijing,
between magnitude of weight loss China), is to describe diabetes man-
and likelihood of diabetes remission. agement patterns and disease evolu-
No member of the control group tion over 3 years for people initiating
experienced ≥15 kg weight loss a second-line glucose-lowering
(P < 0.0001 for comparison), therapy. Dr Mikhail Kosiborod
although 4% (6/149) did achieve dia- (University of Missouri, Kansas City,
betes remission with a mean 5% body MO, USA) presented key findings

© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd 353
Diabetes News

from the program so far (the 3 years 13% of the overall study population, outcomes in people with type 2 dia-
of planned follow-up is ongoing): ranging from 10% in Africa and the betes: Rationale and methods of the
<80% of participants had a recorded Americas to 18% in Europe. Dr Kosi- DISCOVER observational study
program. J Diabetes Complications.
HbA1c assessment, revealing gaps in borod’s main takeaway from these
2017; 31: 1186–96.
screening and monitoring. The data was that a large proportion of 3. Marso SP, Bain SC, Consoli A
HbA1c screening rate was lowest in patients relatively early in the course et al. Semaglutide and cardiovascu-
Africa, at 57%, followed by Southeast of diabetes (mean diabetes duration lar outcomes in patients with type
Asia (61%), ranging up to the Eastern 5.6 years, range 4–7 years) present 2 diabetes. N Engl J Med. 2016;
Mediterranean (94%). When screen- with microvascular disease, macrovas- 375: 1834–44.
ing was defined as HbA1c or fasting 4. Jardine MJ, Mahaffey KW, Neal B
cular disease, or a combination of
et al. The Canagliflozin and Renal
plasma glucose evaluations, the rate both. He listed four correlates for Endpoints in Diabetes with Estab-
increased, but was still <90% globally. both micro- and macrovascular com- lished Nephropathy Clinical Evalua-
Mean HbA1c across the entire global plications: (i) male gender; (ii) older tion (CREDENCE) study rationale,
study population was 8.4%, from a age; (iii) smoking; and (iv) a history design, and baseline characteristics.
high of 8.7% in the Eastern Mediter- of hypoglycemia. He also emphasized Am J Nephrol. 2017; 46: 462–72.
ranean to a low of 8.1% in Europe. that mean worldwide HbA1c for the 5. Neal B, Perkovic V, Mahaffey KW
et al. Canagliflozin and cardiovascu-
Nearly one-third of the population T2D population is far above goal, lar and renal events in type 2 diabetes.
initiating a second-line therapy had and suggested that DISCOVER pro- N Engl J Med. 2017; 377: 644–57.
HbA1c ≥9%, whereas 55% had vides evidence for broad treatment 6. Pratley R, Eldor R, Raji A
HbA1c ≥8% and only 15% met an inertia, given that people starting a et al. Ertugliflozin plus sitagliptin
HbA1c target <7%. The prevalence second diabetes drug exhibited high versus either individual agent over
of microvascular complications HbA1c and frequent complications. 52 weeks in patients with type 2 dia-
(chronic kidney disease, albuminuria, betes mellitus inadequately con-
trolled with metformin: The
retinopathy, retinal laser photocoagu-
VERTIS FACTORIAL randomized
lation, autonomic neuropathy, periph- trial. Diabetes Obes Metab. 2017.
eral neuropathy, or erectile References
https://doi.org/10.1111/dom.13194.
dysfunction) was 18% globally, rang- 1. Lean MEJ, Leslie WS, Barnes AC (in press)
ing from 13% in the Americas to 22% et al. Primary care-led weight man- 7. Dagogo-Jack S, Liu J, Eldor R
in Southeast Asia. Macrovascular agement for remission of type 2 dia- et al. Efficacy and safety of the addi-
complications (coronary artery dis- betes (DiRECT): An open-label, tion of ertugliflozin in patients with
cluster-randomised trial. Lancet. type 2 diabetes mellitus inadequately
ease, stroke, transient ischemic attack,
2017. https://doi.org/10.1016/S0140- controlled with metformin and sita-
carotid artery stenting, carotid endar- 6736(17)33102-1. (in press) gliptin: The VERTIS SITA2 placebo-
terectomy, peripheral artery disease, 2. Linong J, Bonnet F, Charbonnel B controlled randomized study. Diabetes
diabetic foot, amputation, defibrilla- et al. Towards an improved global Obes Metab. 2017. https://doi.org/10.
tor use, or heart failure) appeared in understanding of treatment and 1111/dom.13116. (in press)

Company updates
Adocia (Paris, France) released topline data from the first head-to-head trial of ultra-rapid-acting insulins.
Delivered via pumps to 42 patients with type 1 diabetes (T1D), Adocia’s Phase 3-ready BioChaperone
December 6, 2017: Lispro demonstrated significantly faster offset versus Novo Nordisk’s (Copenhagen, Denmark) Fiasp (faster-
acting insulin aspart), with a late time to half-maximum glucose infusion rate of 210 versus 228 min,
respectively (18-min difference; P = 0.0017). Onset time was similar between the two insulins, with mean

354 © 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd
 Diabetes News

Company updates
metabolic effect within the first hour of 162 versus 154 mg/kg for BioChaperone Lispro versus Fiasp,
respectively (NS). Moreover, Adocia’s candidate was superior to Novo Nordisk’s NovoLog (insulin aspart)
for both onset and offset time. Metabolic effect within the first hour was 63% higher with BioChaperone
Lispro versus NovoLog (162 vs 99 mg/kg, respectively; P < 0.0001). Mean offset time was 232 min with
NovoLog, significantly slower than the 210 min with BioChaperone Lispro (P = 0.002).Adocia will meet with
the US Food and Drug Administration (FDA) sometime next year to discuss a Phase 3 program for
BioChaperone Lispro. The company may seek a dedicated partner before initiating Phase 3.

Zealand (Copenhagen, Denmark) announced the initiation of a Phase 3 pivotal trial for dasiglucagon, its
potential first-in-class liquid-stable glucagon analog. The study is expected to complete in the second half of
2018. If results are positive, FDA submission is planned for 2019. The pivotal trial will evaluate the safety
and efficacy of dasiglucagon administered as a single-dose hypoglycemia rescue treatment for people with
T1D (n = 156). Participants will be randomized to the study drug, placebo, or currently marketed powder
December 7, 2017:
glucagon (which requires reconstitution), and a secondary endpoint will compare efficacy between
dasiglucagon and currently marketed glucagon. Although Zealand plans on commercializing dasiglucagon in
a rescue pen device, this study will use syringes. Zealand has indicated that prior to submitting a New Drug
Application, the company will conduct either an additional Phase 3 trial using dasiglucagon in a rescue pen
device or a small bridging study to show that the pen is as efficacious as a syringe.
Sanofi (Paris, France) announced full FDA approval of Admelog (biosimilar insulin lispro), the first-to-market
biosimilar mealtime insulin in the US; Admelog is a biosimilar formulation of Lilly’s (Indianapolis, IN, USA)
Humalog. This regulatory decision follows the FDA’s tentative approval of Admelog in September 2017
(indicating that the candidate had fulfilled all regulatory requirements but that it could not be launched until
December 11, 2017:
all patent disputes were settled), after which Lilly announced that it would not pursue a patent infringement
lawsuit over Humalog. Sanofi’s announcement did not include specific information about launch timing, but
management has stated recently that Admelog will become available in the US sometime in 2018, even if it
does not make an appreciable sales impact until 2019.
The Committee for Medicinal Products for Human Use (CHMP) recommended Novo Nordisk’s Ozempic
(semaglutide), a once-weekly glucagon-like peptide-1 (GLP-1) agonist, for European Medicine Agency (EMA)
approval. Final marketing authorization for Europe is anticipated in the first quarter of 2018. As part of
European approval, Novo Nordisk has agreed to conduct post-market studies investigating the long-term
effect of semaglutide on retinopathy. This requirement for approval is a reaction to the heightened
December 15, 2017:
retinopathy risk seen in SUSTAIN 6 (hazard ratio [HR] = 1.76; 95% confidence interval [CI] 1.11–2.78),3 a
premarket cardiovascular outcomes trial comparing semaglutide with placebo. Novo Nordisk’s
announcement further highlighted that the European label for Ozempic could include data on superior
weight loss versus comparators and on improved renal outcomes, neither of which made it onto the US
label; FDA approval for Ozempic came earlier in December 2017.
A paper detailing methods for the Canagliflozin and Renal Endpoints in Diabetes with Established
Nephropathy Clinical Evaluation (CREDENCE) trial4 was published in the American Journal of Nephrology.
This study, expected to complete in June 2019, evaluates renal outcomes with Johnson & Johnson’s (New
Brunswick, NJ, USA) sodium-glucose cotransporter 2 (SGLT2) inhibitor Invokana (canagliflozin) in patients
with T2D and comorbid kidney disease. According to the paper, amputations in CREDENCE are being
December 18, 2017: recorded as an adverse event of interest. Precise procedures for data collection were not clearly stipulated.
Trial protocol recommends that patients stop treatment if they experience an amputation-related condition:
critical limb ischemia was the one example given. As background, Invokana was associated with an
increased risk for lower limb amputations in the Canagliflozin and Cardiovascular and Renal Events in Type
2 Diabetes (CANVAS) trial5 and FDA has added a black box warning for amputations to all canagliflozin-
containing medicines.

© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd 355
Diabetes News

Company updates
The FDA approved Merck (Kenilworth, NJ, USA) and Pfizer’s (New York, NY, USA) SGLT2 inhibitor
ertugliflozin for T2D under the brand name Steglatro. This positive decision comes on time with the
expected fourth quarter of 2017, and it makes for a four-product SGLT2 inhibitor class: Steglatro joins Lilly
and Boehringer Ingelheim’s (Ingelheim, Germany) Jardiance (empagliflozin), Invokana (canagliflozin), and
AstraZeneca’s (Cambridge, UK) Farxiga (dapagliflozin). The FDA simultaneously approved Steglujan, a fixed-
dose combination tablet of ertugliflozin with Merck’s dipeptidyl peptidase (DPP)-4 inhibitor Januvia
December 21, 2017:
(sitagliptin) and Segluromet, a fixed-dose combination of ertugliflozin with metformin. All three products are
slated for a US launch in the first quarter of 2018 (Steglatro and Steglujan in January, Segluromet in
February). The combination of ertugliflozin and sitagliptin showed superior efficacy versus either
monotherapy in VERTIS FACTORIAL6 and VERTIS SITA2.7 The list price for Steglatroin the US will be US
$8.94/day (approximately US$268 for a 30-day supply of once-daily tablets), and the same is true for
Segluromet. The list price for Steglujan will be US$17.45/day.

356 © 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd