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Drugs on Pipeline For Management of Diabetes - 495
An Overview

apies to insulin that can improve glycemic control TTP273
without these complications.
Glucagon-like peptide-1 (GLP-1) is a member of
Highly selective inhibitors of sodium–glucose cotrans- the incretin family of neuroendocrine peptide hor-
porter (SGLT) 2, the transporter primarily responsible mones secreted from L-cells of the intestine in
for renal glucose reabsorption, are approved for the response to food ingestion. Though GLP-1 has at-
treatment of type 2 diabetes and under exploration tractive multiple metabolic effects such as sup-
in patients with type 1 diabetes . SGLT1 is the primary pression of excessive glucagon production, de-
transporter for absorption of glucose and galactose in creased food intake, delayed gastric emptying and
the intestine. Sotagliflozin is a novel, orally delivered, improvement of β-cell mass and function, their
small-molecule dual inhibitor of SGLT1 and SGLT2 widespread use is hindered by the route of admin-
that was designed to reduce glucose absorption in istration (injection), and by the high incidenceof
the gastrointestinal (GI) tract via SGLT1 inhibition and gastrointestinal Sideeffects (nauseaandvomiting).
renal glucose reabsorption via SGLT2 inhibition.
TTP273 has been identified as an orally bioavailable,
The study published in journal of diabetes care Jul potent, non-peptide agonist of GLP-1R for the treat-
2015showed that there were no cases of severe hy- ment of type 2 diabetes and is anticipated to provide
poglycemia reported, and numerically less hypogly- excellent glycemic control and an attractive safety
cemic events in the sotagliflozin-treated group com- profile for the treatment of type 2 diabetes.
pared with placebo. Additionally, it has been reported
that treatment with 400 mg sotagliflozin given once A recently-completed 12-week study in 187 patients
daily for 33 patients before breakfast resulted in sig- with T2DM, where notable HbA1c lowering, in addi-
nificant reductions in bolus insulin dose, weight re- tion to a trend for weight loss, was observed with this
duction, significant pre- and postmeal improvements compound compared to Metformin . The incidence
in glucose levels and 0.55% reduction of HbA1c after of gastrointestinal adverse events noted with treat-
29 days of treatment.No patient on sotagliflozin re- ment is very low. The ongoing LOGRA Phase 2 study
ported any genitourinary infections. 3 will evaluate TTP273, for enhanced glycemic control,
weight loss and an attractive safety profile for the
Semaglutide treatment of Type 2 diabetes.

Currently, GLP-1 receptor agonists are available only
as injectables, either once daily or once weekly. Combination of Insulin
Semaglutide is a long-acting GLP-1 receptor agonist Though Insulin, in many forms, is the prime drug
that is also being developed as once weekly dose being used in type 1 and many situations of type 2
and oral version coformulated with the absorption diabetes, it has to be combined with other drugs to
enhancer sodium N-[8-(2-hydroxybenzoy amino] counter its side effects and therapeutic efficacy. One
caprylate. The phase 2 dose-finding study showed such combination in pipeline, is iGlarLixi (100/33)a
HbA and weight reduction were of similar magni- fixed-ratio combination of insulin glargine 100 u/ml
1c
tude to that seen with the injectable GLP-1 receptor and lixisenatide33 mcg/mL, a glucagon-like peptide-1
agonist formulations, and there were no red flags in receptor agonist, for the treatment of type 2 diabe-
terms of safety.Phase 3 trials of injectable semaglu- tes. The mechanisms of action of lixisenatide and
tide have shown that it has a best in class profile insulin glargine are complementary insulin glargine
not just in lowering blood glucose, but also in cutting lowers basal glucose levels throughout the day while
the risk of heart attacks and strokes – the biggest lixisenatide primarily targets glycemic control espe-
long-term danger for diabetes patients. A phase 2 cially PPG excursions. In clinical trials, iGlarLixi was
study(Novel Oral GLP-1 Receptor Agonist Lowers associated with significantly greater reductions from
A1C and Weight in Type 2 Diabetes) randomized 632 baseline in glycated hemoglobin A (A1C) than iGlar
1C
adults with type 2 diabetes (mean duration, 6 years) or lixisenatide alone. Reductions in postprandial glu-
to oral semaglutide (2.5, 5, 10, 20, or 40 mg once cose were also greater with iGlarLixi than with iGlar
daily. Results of this studydone byChristophKapitza or lixisenatide. Gastrointestinal events, frequently
et al concluded that treatment with semaglutide may associated with lixisenatide, were less common with
offer a protective effect on beta cell function. Oral iGlarLixi. 5
semaglutide significantly reduced not only A1C but The IDegLira ,acombination product of insulin de-
also fasting plasma glucose and body weight. This gludec injection and liraglutide injection intended for
novel drug with side effect profile reported only in the market will be provided in a pre-filled pen con-
GIT is awaiting approval from FDA. 4 taining an IDeg/liraglutide ratio of 100 units/3.6 mg

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