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Teneligliptin
The emerging gliptin
Akshata Rao
Medical Services
Diabetes in Indian subcontinent
Retrieved from http://www.cadiresearch.org/topic/diabetes-indians/diabetes-in-the-indian-s...
Choice of agents in current use
Sulphonylureas
Insulin
Thiazolidinediones
Biguanides
Alpha-glucosidase inhibitors
Me...
Each therapy has a drawback
Tripathi 2005, 5th Edition
Nature Reviews 2007 :6 :109-110
Pharmacology and Therapeutics 2010:...
DPP-4 Inhibitors - A major addition
to Diabetes Armamentarium
Major DPP-4 inhibitors currently available :-
Sitagliptin
...
Highest potency
Long half – life
Safety in renal patients
Safety in hepatic patients
Approved by *Ministry of Health, ...
Teneligliptin – Structural features
Introduction of the ‘’anchor lock domain’’, which binds to the S2
extensive subsite - ...
Unique binding capability
Occupies a larger area of
2.08nm2
Effect on the outcome
1500 fold higher
activity
As compared to...
Unique mode of excretion
Teneligliptin excreted
by two modes of
excretion i.e. by liver
and kidney . (Liver -
45.4% and ki...
Teneligliptin Vs other gliptins –
Interaction with DPP-4 enzymes.
Journal of Diabetes Mellitus, 2016, 6, 113-131
Teneligliptin Vs other gliptins –
Pharmacokinetic comparison
Journal of Diabetes Mellitus, 2016, 6, 113-131
Teneligliptin in renally compromised
patients
In special
population
(Renal
Impairment)
Design Prospective, non-randomized study with 43 diabetic ESRD
patients ; Tenelig...
Teneligliptin significantly improves the
glycemic states in Diabetic ESRD patients
Blood glucose decreased significantly ...
Teneligliptin also improves glycemic states in patients
switching from conventional Oral Anti-Diabetic drugs
Blood glucose...
Conclusion
• Teneligliptin is well tolerated, safe, and significantly improves glycemic
control in diabetic patients with ...
Teneligliptin in Indian patients
Study of Anti-hyperglycemic Activity of
Teneligliptin in Patients of T2DM
Design Uncontrolled, open label, observational s...
Teneligliptin Vs other gliptins
Impact of teneligliptin on oxidative
stress and endothelial function in type 2
diabetes patients with chronic kidney
disea...
Results
Baseline After 3 months
Fasting blood
glucose (mg/dl)
172.4 124.5
Post prandial blood
glucose
225.5 176.4
HbA1C (%...
Results
Cardiovasc Diabetol (2016) 15:76
Results
Changes in RHI Changes in d-ROMs
Cardiovasc Diabetol (2016) 15:76
Conclusion
• Teneligliptin exhibits beneficial effects on both oxidative stress and
endothelial function in Japanese patie...
Efficacy of linagliptin and teneligliptin for
glycemic control in type 2 diabetic
patients with chronic kidney disease:
as...
Results
Twenty-four-hour mean sensor
glucose levels before treatment and
after 6 days of treatment with
linagliptin/ tenel...
Conclusion
• In type 2 diabetes patients complicated by CKD, the effects of treatment
with linagliptin and teneligliptin o...
Design Open label , non-randomised parallel group study (8 subjects in
each group)
Healthy
Mild hepatic impairment
Moderat...
Teneligliptin well-tolerated by patients
with hepatic impairment
Parameter Group Ratio of
Geometric mean
90% CI (%)
AUC 0-...
In special
population
(Cardiac
patients)
Heart Vessels. 2015 Aug 13.
Major findings of the study
An additional treatment ...
In special
population
(Cardiac
patients)
International Journal of General Medicine 2016:9 65–71
Effects of teneligliptin o...
Future research on possible benefits of
Teneligliptin
Obesity
Title of the study Year of Publishing Teneligliptin effects
...
Future research on possible benefits of
Teneligliptin
Non-alcoholic Fatty Liver disease
Title of the study Year of Publish...
Teneligliptin – Road ahead
Teneligliptin –Clinical trial in cardiac
patients
The trial is expected to be completed by June 2019
Retrieved from https:...
Tenegliptin – Dosage and Administration
• Indication
• Oral Teneligliptin is approved as an add-on for treatment of adults...
Precautions while administering
Teneligliptin
• Teneligliptin should be used with caution in patients with severe hepatic
...
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Teneligliptin the next generation gliptin

Teneligliptin , one of the emerging gliptins have established its prowess among the gliptin giants like Sitagliptin Vildagliptin and Linagliptin. Proven to be safe in renally compromised patients, this one is to watch out for.

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Teneligliptin the next generation gliptin

  1. 1. Teneligliptin The emerging gliptin Akshata Rao Medical Services
  2. 2. Diabetes in Indian subcontinent Retrieved from http://www.cadiresearch.org/topic/diabetes-indians/diabetes-in-the-indian-subcontinent
  3. 3. Choice of agents in current use Sulphonylureas Insulin Thiazolidinediones Biguanides Alpha-glucosidase inhibitors Meglitinides
  4. 4. Each therapy has a drawback Tripathi 2005, 5th Edition Nature Reviews 2007 :6 :109-110 Pharmacology and Therapeutics 2010:125; 328-361
  5. 5. DPP-4 Inhibitors - A major addition to Diabetes Armamentarium Major DPP-4 inhibitors currently available :- Sitagliptin Vildagliptin Saxagliptin Linagliptin
  6. 6. Highest potency Long half – life Safety in renal patients Safety in hepatic patients Approved by *Ministry of Health, Labour and Welfare (MHLW) Japanese Pharmaceutical and Medical Devices Agency (PMDA) in 2012 Accessed from http://www.pmda.go.jp/files/000153594.pdf Ministry of Health, Labour and Welfare (MHLW) Japanese Pharmaceutical and Medical Devices Agency - Both are governing bodies which is responsible for final drug approval in Japan Teneligliptin – Novel and potent addition to gliptin category Important features to be noted
  7. 7. Teneligliptin – Structural features Introduction of the ‘’anchor lock domain’’, which binds to the S2 extensive subsite - Higher potency and selectivity Forms a stable gliptin-DPP-4 enzyme complex due rigid 5 ring “J structure - Longer Half life Carbonyl group derived from the peptide mimetic, forms a hydrogen bond (strongest bond) DPP4 enzyme - Higher potency Biochemical and Biophysical Research Communications 434 (2013) 191–196
  8. 8. Unique binding capability Occupies a larger area of 2.08nm2 Effect on the outcome 1500 fold higher activity As compared to Vildagliptin and Saxagliptin 5 fold higher activity As compared to Sitagliptin
  9. 9. Unique mode of excretion Teneligliptin excreted by two modes of excretion i.e. by liver and kidney . (Liver - 45.4% and kidney - 46.5%
  10. 10. Teneligliptin Vs other gliptins – Interaction with DPP-4 enzymes. Journal of Diabetes Mellitus, 2016, 6, 113-131
  11. 11. Teneligliptin Vs other gliptins – Pharmacokinetic comparison Journal of Diabetes Mellitus, 2016, 6, 113-131
  12. 12. Teneligliptin in renally compromised patients
  13. 13. In special population (Renal Impairment) Design Prospective, non-randomized study with 43 diabetic ESRD patients ; Teneligliptin 20 mg/day (n=14) and Control group ( n= 29) Control group treated with voglibose, vildagliptin, miglitol, Meglitinides Duration 28 weeks Patient characteristic s ESRD diabetic patients with Serum Creatinine levels* (Teneligliptin group = 9.1mg/dl and Control group = 10.3 mg/dl End-points Blood glucose levels , Glycated Albumin levels (GA) and HbA1C(%) Normal creatinine levels *- 0.6 to 1.2 milligrams (mg) per deciliter (dL) in adult males and 0.5 to 1.1 milligrams per deciliter in adult females Int Urol Nephrol (2014) 46:427–432 Safety and efficacy of teneligliptin: a novel DPP-4 inhibitor for hemodialysis patients with type 2 diabetes.
  14. 14. Teneligliptin significantly improves the glycemic states in Diabetic ESRD patients Blood glucose decreased significantly in the teneligliptin group from 4 weeks GA level in the teneligliptin group dropped significantly after 4 weeks HbA1c in the teneligliptin group declined significantly from 8 weeks P<0.05 P<0.05 p = 0.057 Int Urol Nephrol (2014) 46:427–432 Duration – 28 weeks
  15. 15. Teneligliptin also improves glycemic states in patients switching from conventional Oral Anti-Diabetic drugs Blood glucose level decreased 21–60 mg/dl at 28 weeks after teneligliptin administration. GA dropped 1.7–2.3 % by 28 weeks and HbA1c fell 0.3–0.8 % by 24 weeks. Int Urol Nephrol (2014) 46:427–432
  16. 16. Conclusion • Teneligliptin is well tolerated, safe, and significantly improves glycemic control in diabetic patients with ESRD. • No serious side effects or hypoglycemia relating to teneligliptin is seen during the study. • Teneligliptin 20 mg is probably stronger than Vildagliptin 50 mg for dialysis patients. • Teneligliptin is expected to be a powerful DPP-4 inhibitor of ESRD. Int Urol Nephrol (2014) 46:427–432
  17. 17. Teneligliptin in Indian patients
  18. 18. Study of Anti-hyperglycemic Activity of Teneligliptin in Patients of T2DM Design Uncontrolled, open label, observational study with patients who were uncontrolled on metformin were selected. Teneligliptin 20 mg/day was added to current treatment. Duration 12 weeks Patient characteristic s Patients of T2DM attending OPD of Dhanashree Hospital, Pune were included in the study after obtaining informed written consent End-points Fasting blood sugar level, Post prandial blood sugar level and HbA1C (%) Indian J Pharmacol. 2015 Dec; 47(Suppl 1): S57–S177.
  19. 19. Teneligliptin Vs other gliptins
  20. 20. Impact of teneligliptin on oxidative stress and endothelial function in type 2 diabetes patients with chronic kidney disease: a case–control study Cardiovasc Diabetol (2016) 15:76 Design Open-label, prospective, randomized study with 45 diabetic CKD patients who received sitagliptin for at least 12 months were randomized to either continue sitagliptin (n = 23) or switch to teneligliptin (n = 22) Duration 24 weeks Patient characteristic s type 2 diabetes with (HbA1c) >6.5 %, CKD (eGFR) <60 mL/min/1.73 m2 or microalbuminuria >30 mg/g Cr] [14], and treatment with sitagliptin for 1 year or longer End-points HbA1c, eGFR, or urinary albumin excretion levels, endothelial function by reactive hyperaemia index (RHI), reactive oxygen metabolites (ROMs) measured by the d-ROMS test
  21. 21. Results Baseline After 3 months Fasting blood glucose (mg/dl) 172.4 124.5 Post prandial blood glucose 225.5 176.4 HbA1C (%) 9.5 8.6 Cardiovasc Diabetol (2016) 15:76 Conclusion: Teneligliptin can be considered as an effective alternative for add-on treatment in patients of T2DM uncontrolled on metformin monotherapy.
  22. 22. Results Cardiovasc Diabetol (2016) 15:76
  23. 23. Results Changes in RHI Changes in d-ROMs Cardiovasc Diabetol (2016) 15:76
  24. 24. Conclusion • Teneligliptin exhibits beneficial effects on both oxidative stress and endothelial function in Japanese patients with type 2 diabetes and CKD. • Teneligliptin exhibits beneficial effects on both oxidative stress and endothelial function in Japanese patients with type 2 diabetes and CKD. • The antioxidative effect of Teneligliptin is brought about by the sulphur atom present in the molecule Cardiovasc Diabetol (2016) 15:76
  25. 25. Efficacy of linagliptin and teneligliptin for glycemic control in type 2 diabetic patients with chronic kidney disease: assessment by continuous glucose monitoring; a pilot study Diabetology International pp 1-7 First online: 09 March 2016 Design randomized and crossover in design in 13 type 2 diabetes patients with CKD treated with teneligliptin at 20 mg/day or linagliptin at 5 mg/day for 6 days then switched to the other agent for another 6 days.) Duration 12 days Patient characteristic s type 2 diabetes patients with CKD who maintained glycosylated hemoglobin (HbA1c) levels at <9 % by diet and exercise and had estimated glomerular filtration rates (eGFRs) 60 ml/min 1.73 m2. End-points Mean amplitude of glucose excursions (MAGE)
  26. 26. Results Twenty-four-hour mean sensor glucose levels before treatment and after 6 days of treatment with linagliptin/ teneligliptin in 13 patients. Mean amplitude of glycemic excursions (MAGE) before treatment and after 6 days treatment with linagliptin/teneligliptin. Values are mean ± standard deviation. **P<0.01, vs before treatment no significant difference between the two groups (p = 0.05). Diabetology International pp 1-7 First online: 09 March 2016
  27. 27. Conclusion • In type 2 diabetes patients complicated by CKD, the effects of treatment with linagliptin and teneligliptin on CGM-based MAGE were comparable. • Because both agents significantly reduced the 24-h mean sensor glucose levels and AUC 180 but did not increase the incidence of hypoglycemia, they have comparable efficacy and safety in type 2 diabetes patients complicated by CKD. Diabetology International pp 1-7 First online: 09 March 2016
  28. 28. Design Open label , non-randomised parallel group study (8 subjects in each group) Healthy Mild hepatic impairment Moderate hepatic impairment Evaluation paramete rs All Teneligliptin Pharmacokinetic parameters and safety parameters In special population (Hepatic impairment) Clinical Pharmacology in Drug Development Volume 3, Issue 4, pages 290–296, July/August 2014 Objective – To determine the pharmacokinetic and safety of single oral administration of therapeutic doses of 20 mg Teneligliptin in subjects with mild and moderate hepatic impairment as compared to healthy subjects Pharmacokinetics and safety of teneligliptin in subjects with hepatic impairment
  29. 29. Teneligliptin well-tolerated by patients with hepatic impairment Parameter Group Ratio of Geometric mean 90% CI (%) AUC 0-∞ Mild 145.85 122.13-174.17 Moderate 159.41 133-190.37 FDA-recommended “dose-adjustment” boundary of 200% The AUC for Teneligliptin is within the dose adjustment limit set by FDA No dose adjustment required for patients with mild to moderated hepatic impairment Clinical Pharmacology in Drug Development Volume 3, Issue 4, pages 290–296, July/August 2014
  30. 30. In special population (Cardiac patients) Heart Vessels. 2015 Aug 13. Major findings of the study An additional treatment with Teneligliptin improved Left ventricular diastolic function and endothelial function. Teneligliptin treatment exerts cardio- protective effects in T2DM patients with LV dysfunction at an early stage. An increase in the serum levels of adiponectin* after 3 months of Teneligliptin treatment is seen adiponectin*- adiponectin plays a role of antiatherosclerotic, antidiabetic, and anti-inflammatory effects A high plasma level of adiponectin leads to a decrease in cardiovascular events Teneligliptin improves left ventricular diastolic function and endothelial function in patients with diabetes.
  31. 31. In special population (Cardiac patients) International Journal of General Medicine 2016:9 65–71 Effects of teneligliptin on PDMPs and PAI-1 in patients with diabetes on hemodialysis
  32. 32. Future research on possible benefits of Teneligliptin Obesity Title of the study Year of Publishing Teneligliptin effects The novel DPP-4 inhibitor teneligliptin prevent s high-fat diet-induced obesity accompanied with increased energy expenditure in mice. Eur J Pharmacol. 2014 Jan 15;723:207-15 Adipocyte hypertrophy and hepatic steatosis induced by a high-fat diet were suppressed by teneligliptin. Teneligliptin improves metabolic abnormalities in a mouse model of postmenopausal obesity. J Endocrinol. 2015 Oct;227(1):25-36. Teneligliptin effectively ameliorated the characteristics of metabolic abnormalities associated with postmenopausal obesity.. Hepatic steatosis was also markedly improved.
  33. 33. Future research on possible benefits of Teneligliptin Non-alcoholic Fatty Liver disease Title of the study Year of Publishing Teneligliptin effects The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice Int J Mol Sci. 2015 Dec; 16(12): 29207–29218.  Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin- treated mice (p < 0.05).  Teneligliptin increased hepatic expression levels of phosphorylated AMP- activated protein kinase (AMPK) protein.
  34. 34. Teneligliptin – Road ahead
  35. 35. Teneligliptin –Clinical trial in cardiac patients The trial is expected to be completed by June 2019 Retrieved from https://clinicaltrials.gov/ct2/show/NCT02449330
  36. 36. Tenegliptin – Dosage and Administration • Indication • Oral Teneligliptin is approved as an add-on for treatment of adults with type 2 diabetes mellitus patients who have not responded adequately to treatment with diet and exercise or addition of other anti-diabetic agents such as biguanides, sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors or insulin. • Dosage • The recommended dosage of Teneligliptin is 20 mg once daily. • Teneligliptin may be administered irrespective of food, preferably before breakfast. • It is advisable to uptitrate the dosage to 40 mg once daily in patients who do not achieve adequate glycemic control as required. Journal of Diabetes Mellitus, 2016, 6, 113-131
  37. 37. Precautions while administering Teneligliptin • Teneligliptin should be used with caution in patients with severe hepatic impairment & those with heart failure (NYHA Class III - IV), because of a lack of clinical experience in these populations. • Teneligliptin should not be used in patients with history of pancreatitis. If the patient is already on sulfonylurea & addition of gliptin is considered, in such cases the dose of sulfonylurea should be halved & then up- titrated as required to reduce the risk of hypoglycaemia. • There may be chances of hypoglycemia on co-administration of Teneligliptin with insulin & hence dosage reduction may be required Journal of Diabetes Mellitus, 2016, 6, 113-131
  38. 38. THANK YOU!!!!

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