Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-77c89778f8-7drxs Total loading time: 0 Render date: 2024-07-19T22:24:41.900Z Has data issue: false hasContentIssue false

2 - TRANSLATIONAL MEDICINE AND ITS IMPACT ON DIABETES DRUG DEVELOPMENT

Published online by Cambridge University Press:  04 April 2011

By
Roberto A. Calle  and
Ann E. Taylor
Edited by
Bruce H. Littman  and
Rajesh Krishna
Roberto A. Calle
Affiliation:
Pfizer Pharmatherapeutics Research and Development
Ann E. Taylor
Affiliation:
Novartis
Bruce H. Littman
Affiliation:
Translational Medicine Associates
Rajesh Krishna
Affiliation:
Merck Research Laboratories
Get access

Summary

Introduction

Type 2 diabetes is one of the largest medical burdens in the United States. At present it is estimated that 23.6 million people in the United States have diabetes (7.8% of the population) of which 5.7 million remain undiagnosed. Of this total, approximately 95% have type 2 diabetes. In addition to insulin, eight different drug classes are available for the treatment of type 2 diabetes. In spite of all these drugs being available, many of them generic, only 49.8% of patients reach the American Diabetes Association–recommended targets for glucose control. Moreover, many patients require the addition of a second therapy to maintain glucose control. Thirty-six percent require a second therapy with a mean time to failure from start of initial therapy of 1.51 years. Thus, many patients require multiple medications and often eventual insulin replacement. Furthermore, many of the existing drugs have characteristics and potential adverse effects that make them less than ideal.

Macrovascular and microvascular complications continue to take a heavy toll on patients with diabetes. An estimated 57.9% of people with type 2 diabetes have one or more complications. As a nation, the United States spends $57.1 billion a year in health care related to diabetes and its complications. With an estimated 57 million people now having prediabetes, this metabolic pandemic can only be expected to grow unless serious steps are taken at the public health and drug development levels. Therefore, the need for better drugs for type 2 diabetes is now stronger than ever.

Type
Chapter
Information
Translational Medicine and Drug Discovery , pp. 35 - 61
Publisher: Cambridge University Press
Print publication year: 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

,Centers for Disease Control and Prevention (CDC). (2008). National diabetes fact sheet: General information and national estimates on diabetes in the United States, 2007. Atlanta, GA: U.S. Department of Health and Human Services, CDC.Google Scholar
Resnick, HE, Foster, GL, Bardsley, J, & Ratner, RE. (2006). Achievement of American Diabetes Association clinical practice recommendations among U.S. adults with diabetes, 1999–2002: The National Health and Nutrition Examination Survey. Diabetes Care. 29(3), 531–537.CrossRefGoogle ScholarPubMed
Riedel, AA, Heien, H, Wogen, J, & Plauschinat, CA. (2007). Loss of glycemic control in patients with type 2 diabetes mellitus who were receiving initial metformin, sulfonylurea, or thiazolidinedione monotherapy. Pharmacotherapy. 27(8), 1102–1110.CrossRefGoogle ScholarPubMed
Philippe, J, & Raccah, D. (2009). Treating type 2 diabetes: How safe are current therapeutic agents? Int. J. Clin. Practice. 63(2), 321–332.CrossRefGoogle ScholarPubMed
,American Association of Clinical Endocrinologists (AACE). (2007). State of diabetes complications in America: A comprehensive report Issued by the AACE. Available at: http://multivu.prnewswire.com/mnr/AACE/2007/docs/Diabetes_Complications_Report.pdf
Gonzalez-Ortiz, M, Hernandez-Salazar, E, & Martinez-Abundis, E. (2005). Effect of the administration of a single dose of nateglinide on insulin secretion at two different concentrations of glucose in healthy individuals. J. Diabetes Complicat. 19(6), 356–360.CrossRefGoogle ScholarPubMed
Hirose, T, Mizuno, R, & Yoshimoto, T. (2002). The effects of nateglinide following oral glucose load in impaired glucose tolerance subjects: Rapid insulin stimulation by nateglinide in IGT subjects. Endocr. J. 49(6), 649–652.CrossRefGoogle ScholarPubMed
Hammarstedt, A, Sopasakis, VR, Gogg, S, Jansson, PA, & Smith, U. (2005). Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects. Diabetologia. 48(1), 96–104.CrossRefGoogle ScholarPubMed
Rasouli, N, Raue, U, Miles, LM, Lu, T, Di Gregorio, GB, Elbein, SC, et al. (2005). Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue. Am. J. Physiol. Endocrinol. Metab. 288(5), E930–E934.CrossRefGoogle ScholarPubMed
Johanson, EH, Jansson, PA, Gustafson, B, Sandqvist, M, Taskinen, MR, Smith, U, et al. (2005). No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes. Diabetes Metab. Res. Rev. 21(4), 376–381.CrossRefGoogle ScholarPubMed
Dominiczak MH, Smith, , McNaught, J, & Paterson, KR. (1998). Assessment of past glycemic control. Measure fructosamine, hemoglobin A1, or both? Diabetes Care. 11(4), 359–360.Google Scholar
Johnson, RN, Metcalf, PA, & Baker, JR. (1983). Fructosamine: A new approach to the estimation of serum glycosylprotein. An index of diabetic control. Clin. Chim. Acta. 127(1), 87–95.CrossRefGoogle ScholarPubMed
Dungan, KM. (2008). 1,5-anhydroglucitol (GlycoMark) as a marker of short-term glycemic control and glycemic excursions. Expert Rev. Mol. Diagn. 8(1), 9–19.CrossRefGoogle ScholarPubMed
Palmer, JP, Fleming, GA, Greenbaum, CJ, Herold, KC, Jansa, LD, Kolb, H, et al. (2004). C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function. Diabetes. 53(1), 250–264.CrossRefGoogle ScholarPubMed
Steffes, MW, Sibley, S, Jackson, M, & Thomas, W. (2003). Beta-cell function and the development of diabetes-related complications in the Diabetes Control and Complications Trial. Diabetes Care. 26(3), 832–836.CrossRefGoogle ScholarPubMed
Inoue, I, Takahashi, K, Katayama, S, Harada, Y, Negishi, K, Ishii, J, et al. (1996). A higher proinsulin response to glucose loading predicts deteriorating fasting plasma glucose and worsening to diabetes in subjects with impaired glucose tolerance. Diabet. Med. 13(4), 330–336.3.0.CO;2-L>CrossRefGoogle ScholarPubMed
Larsson, H, & Ahren, B. (1999). Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance. J. Clin. Endocrinol. Metab. 84(6), 2068–2074.Google Scholar
Pradhan, AD, Manson, JE, Meigs, JB, Rifai, N, Buring, JE, Liu, S, et al. (2003). Insulin, proinsulin, proinsulin:insulin ratio, and the risk of developing type 2 diabetes mellitus in women. Am. J. M. 114(6), 438–444.CrossRefGoogle ScholarPubMed
Hanley, AJ, Zinman, B, Sheridan, P, Yusuf, S, Gerstein, HC, & Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) Investigators. (2010). Effect of rosiglitazone and ramipril on beta-cell function in people with impaired glucose tolerance or impaired fasting glucose. Diabetes Care. 33(3), 608–613.CrossRefGoogle ScholarPubMed
Smith, SA, Porter, , Biswas, N, & Freed, MI. (2004). Rosiglitazone, but not glyburide, reduces circulating proinsulin and the proinsulin:insulin ratio in type 2 diabetes. J. Clin. Endocrinol. Metab. 89(12), 6048–6053.CrossRefGoogle Scholar
Cobelli, C, Toffolo, GM, Man, CD, Campioni, M, Denti, P, Caumo, A, et al. (2007). Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. Am. J. Physiol. Endocrinol. Metab. 293(1), E1–E15.CrossRefGoogle ScholarPubMed
Roden, M. (2007). Clinical Diabetes Research: Methods and Techniques. First ed. West Sussex: John Wiley & Sons Ltd.CrossRefGoogle Scholar
Chan, JM, Rimm, EB, Colditz, GA, Stampfer, MJ, & Willett, WC. (1994). Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 17(9), 961–969.CrossRefGoogle ScholarPubMed
Colditz, GA, Willett, WC, Rotnitzky, A, & Manson, JE. (1995). Weight gain as a risk factor for clinical diabetes mellitus in women. Ann. Intern. Med. 122(7), 481–486.CrossRefGoogle ScholarPubMed
Ferrannini, E, Natali, A, Bell, P, Cavallo-Perin, P, Lalic, N, & Mingrone, G. (1997). Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J. Clin. Invest. 100(5), 1166–1173.CrossRefGoogle Scholar
Ford, ES, Williamson, DF, & Liu, S. (1997). Weight change and diabetes incidence: Findings from a national cohort of US adults. Am. J. Epidemiol. 146(3), 214–222.CrossRefGoogle ScholarPubMed
Anderson, JW, Kendall, CW, & Jenkins, DJ. (2003). Importance of weight management in type 2 diabetes: Review with meta-analysis of clinical studies. J. Am. Coll. Nutr. 22(5), 331–339.CrossRefGoogle ScholarPubMed
,The Look AHEAD Research Group. (2007). Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: One-year results of the Look AHEAD Trial. Diabetes Care. 30(6), 1374–1383.CrossRefGoogle Scholar
U.S. Department of Health and Human Services, Division of Metabolism and Endocrinology Products, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). (2008). Guidance for industry: Diabetes mellitus: Developing drugs and therapeutic biologics for treatment and prevention. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071627.pdf
Franz, MJ. (2007). The dilemma of weight loss in diabetes. Diabetes Spectr. 20(3), 133–136.CrossRefGoogle Scholar
Lloret-Linares, C, Greenfield, JR, & Czernichow, S. (2008). Effect of weight-reducing agents on glycaemic parameters and progression to type 2 diabetes: A review. Diabetic Med. 25(10), 1142–1150.CrossRefGoogle ScholarPubMed
Morrish, NJ, Wang, SL, Stevens, LK, Fuller, JH, & Keen, H. (2001). Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 44(Suppl 2), S14–S21.CrossRefGoogle ScholarPubMed
,American Diabetes Association. (2009). Standards of medical care in diabetes–2009. Diabetes Care. 32(Suppl 1), S13–S61.CrossRefGoogle Scholar
Imperatore, G, Cadwell, BL, Geiss, L, Saadinne, JB, Williams, , Ford, ES, et al. (2004). Thirty-year trends in cardiovascular risk factor levels among US adults with diabetes: National Health and Nutrition Examination Surveys, 1971–2000. Am. J. Epidemiol. 160(6), 531–539.CrossRefGoogle ScholarPubMed
Jacobs, MJ, Kleisli, T, Pio, JR, Malik, S, L'Italien, GJ, Chen, RS, et al. (2005). Prevalence and control of dyslipidemia among persons with diabetes in the United States. Diabetes Res. Clin. Pract. 70(3), 263–269.CrossRefGoogle ScholarPubMed
Pai, JK, Pischon, T, Ma, J, Manson, JE, Hankinson, SE, Joshipura, K, et al. (2004). Inflammatory markers and the risk of coronary heart disease in men and women. N. Engl. J. Med. 351(25), 2599–2610.CrossRefGoogle ScholarPubMed
Ridker, PM, Cannon, CP, Morrow, D, Rifai, N, Rose, LM, McCabe, CH, et al. (2005). C-reactive protein levels and outcomes after statin therapy. N. Engl. J. Med. 352(1), 20–28.CrossRefGoogle ScholarPubMed
Ridker, PM, Danielson, E, Fonseca, FA, Genest, J, Gotto, AM Jr, Kastelein, JJ, et al. (2009). Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: A prospective study of the JUPITER Trial. Lancet. 373(9670), 1175–1182.CrossRefGoogle ScholarPubMed
Kahn, SE. (2003). The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 46(1), 3–19.CrossRefGoogle ScholarPubMed
Festa, A, Williams, K, D'Agostino, R Jr, Wagenknecht, , & Haffner, SM. (2006). The natural course of beta-cell function in nondiabetic and diabetic individuals: The Insulin Resistance Atherosclerosis Study. Diabetes. 55(4), 1114–1120.CrossRefGoogle ScholarPubMed
Jensen, CC, Cnop, M, Hull, RL, Fujimoto, WY, Kahn, SE, & the American Diabetes Association GENNID Study Group. (2002). Beta-cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the U.S. Diabetes. 51(7), 2170–2178.CrossRefGoogle ScholarPubMed
Weyer, C, Bogardus, C, Mott, DM, & Pratley, LE. (1999). The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J. Clin. Invest. 104(6), 787–794.CrossRefGoogle ScholarPubMed
,U.K. Prospective Diabetes Study Group. (1995). U.K. Prospective Diabetes Study 16. Overview of 6 years' therapy of type II diabetes: A progressive disease. Diabetes. 44(11), 1249–1258.CrossRefGoogle Scholar
Kahn, SE, Haffner, SM, Heise, MA, Herman, WH, Holman, RR, Jones, NP, et al. (2006). Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N. Engl. J. Med. 355(23), 2427–2443.CrossRefGoogle ScholarPubMed
Matthews, DR, Hosker, JP, Rudenski, AS, Naylor, BA, Treacher, DF, & Turner, RC. (1985). Homeostasis model assessment: Insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28(7), 412–419.CrossRefGoogle ScholarPubMed
Ahren, B, & Pacini, G. (2004). Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies. Eur. J. Endocrinol. 150(2), 97–104.CrossRefGoogle ScholarPubMed
Bergman, RN. (2005). Minimal model: Perspective from 2005. Horm. Res. Paediatr. 64(Suppl 3), 8–15.CrossRefGoogle ScholarPubMed
Bunck, MC, Diamant, M, Cornér, A, Eliasson, B, Malloy, JL, Shaginian, RM, et al. (2009). One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients. Diabetes Care. 32(5), 762–768.CrossRefGoogle ScholarPubMed
Fehse, F, Trautmann, M, Holst, JJ, Halseth, AE, Nanayakkara, N, Nielsen, LL, et al. (2005). Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes. J. Clin. Endocrinol. Metab. 90(11), 5991–5997.CrossRefGoogle ScholarPubMed
Gastaldelli, A, Ferrannini, E, Miyazaki, Y, Matsuda, M, Mari, A, & DeFronzo, RA. (2007). Thiazolidinediones improve beta-cell function in type 2 diabetic patients. Am. J. Physiol. Endocrinol. Metab. 292(3), E871–E883.CrossRefGoogle ScholarPubMed
Freeby, M, Goland, R, Ichise, M, Maffei, A, Leibel, R, & Harris, P. (2008). VMAT2 quantitation by PET as a biomarker for beta-cell mass in health and disease. Diabetes Obes. Metab. 10(Suppl 4), 98–108.CrossRefGoogle ScholarPubMed
Hirshberg, B, Qiu, M, Cali, AM, Sherwin, R, Constable, T, Calle, RA, et al. (2009). Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging. Diabetologia. 52(8), 1561–1565.CrossRefGoogle ScholarPubMed
Medarova, Z, & Moore, A. (2009). MRI as a tool to monitor islet transplantation. Nat. Rev. Endocrinol. 5(8), 444–452.CrossRefGoogle ScholarPubMed
Robertson, RP. (2007). Estimation of beta-cell mass by metabolic tests. Diabetes. 56(10), 2420–2424.CrossRefGoogle ScholarPubMed
U.S. Department of Health and Human Services, Division of Metabolism and Endocrinology Products, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). (2008). Guidance for industry: Diabetes mellitus – evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071627.pdf
Colhoun, HM, Betteridge, DJ, Durrington, PN, Hitman, GA, Neil, HA, Livingstone, SJ, et al. (2004). Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled trial. Lancet. 364(9435), 685–696.CrossRefGoogle ScholarPubMed
Jenny, NS, Tracy, RP, Ogg, MS, Luong, , Kuller, LH, Arnold, AM, et al. (2002). In the elderly, interleukin-6 plasma levels and the -174G>C polymorphism are associated with the development of cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 22(12), 2066–2071.CrossRefGoogle ScholarPubMed
Koenig, W, Khuseyinova, N, Baumert, J, Thorand, B, Loewel, H, Chambless, L, et al. (2006). Increased concentrations of C-reactive protein and IL-6 but not IL-18 are independently associated with incident coronary events in middle-aged men and women: Results from the MONICA/KORA Augsburg Case-Cohort Study, 1984–2002. Arterioscler. Thromb. Vasc. Biol. 26(12), 2745–2751.CrossRefGoogle Scholar
Juonala, M, Viikari, JS, Laitinen, T, Marniemi, J, Helenius, H, Rönnemma, T, et al. (2004). Interrelations between brachial endothelial function and carotid intima-media thickness in young adults: The Cardiovascular Risk in Young Finns Study. Circulation. 110(18), 2918–2923.CrossRefGoogle ScholarPubMed
Yeboah, J, Crouse, JR, Hsu, F-C, Burke, GL, & Herrington, DM. (2007). Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: The Cardiovascular Health Study. Circulation. 115(18), 2390–2397.CrossRefGoogle ScholarPubMed
Hsue, PY, Hunt, PW, Wu, Y, Schnell, A, Ho, JE, Hatano, H, et al. (2009). Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients. AIDS. 23(15), 2021–2027. 10.1097/QAD.0b013e32832e7140.CrossRefGoogle ScholarPubMed
Bots, ML, Westerink, J, Rabelink, TJ, & Koning, EJP. (2005). Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: Effects of technical aspects of the FMD measurement on the FMD response. Eur. Heart J. 26(4), 363–368.CrossRefGoogle ScholarPubMed
,The Action to Control Cardiovascular Risk in Diabetes Study Group. (2008). Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 358(24), 2545–2559.CrossRefGoogle Scholar
Skyler, JS, Bergenstal, R, Bonow, RO, Buse, J, Deedwania, P, Gale, EAM, et al. (2009). Intensive glycemic control and the prevention of cardiovascular events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials. Circulation. 32(1), 187–192.Google ScholarPubMed
Duckworth, W, Abraira, C, Moritz, T, Reda, D, Emanuele, N, Reaven, PD, et al. (2008). Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med. 360(2), 129–139.CrossRefGoogle ScholarPubMed
,American Diabetes Association Workgroup on Hypoglycemia. (2005). Defining and reporting hypoglycemia in diabetes: A report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 28(5), 1245–1249.CrossRefGoogle Scholar
Evans, ML, Pernet, A, Lomas, J, Jones, J, & Amiel, SA. (2000). Delay in onset of awareness of acute hypoglycemia and of restoration of cognitive performance during recovery. Diabetes Care. 23(7), 893–897.CrossRefGoogle ScholarPubMed
Nauck, MA, Heimesaat, MM, Behle, K, Holst, JJ, Nauck, MS, Ritzel, R, et al. (2002). Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J. Clin. Endocrinol. Metab. 87(3), 1239–1246.CrossRefGoogle ScholarPubMed
Burkey, BF, Li, X, Bolognese, L, Balkan, B, Mone, M, Russell, M, et al. (2005). Acute and chronic effects of the incretin enhancer vildagliptin in insulin-resistant rats. J. Pharmacol. Exp. Ther. 315(2), 688–695.CrossRefGoogle ScholarPubMed
Hu, P, Yin, Q, Deckert, F, Jiang, J, Liu, D, Kjems, L, et al. (2009). Pharmacokinetics and pharmacodynamics of vildagliptin in healthy Chinese volunteers. J. Clin. Pharmacol. 49(1), 39–49.CrossRefGoogle ScholarPubMed
Basu, R, Singh, RJ, Basu, A, Chittilapilly, EG, Johnson, CM, Toffolo, G, et al. (2004). Splanchnic cortisol production occurs in humans: Evidence for conversion of cortisone to cortisol via the 11-beta hydroxysteroid dehydrogenase (11beta-hsd) type 1 pathway. Diabetes. 53(8), 2051–2059.CrossRefGoogle ScholarPubMed
Morton, NM, Holmes, MC, Fiévet, C, Staels, B, Tailleux, A, Mullins, JJ, et al. (2001). Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11-beta-hydroxysteroid dehydrogenase type 1 null mice. J. Biol. Chem. 276(44), 41293–41300.CrossRefGoogle ScholarPubMed
Morton, NM, Paterson, JM, Masuzaki, H, Holmes, MC, Staels, B, Fiévet, C, et al. (2004). Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11-beta-hydroxysteroid dehydrogenase type 1-deficient mice. Diabetes. 53(4), 931–938.CrossRefGoogle ScholarPubMed
Hermanowski-Vosatka, A, Balkovec, JM, Cheng, K, Chen, HY, Hernandez, M, Koo, GC, et al. (2005). 11beta-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice. J. Exp. Med. 202(4), 517–527.CrossRefGoogle ScholarPubMed
Bhat, BG, Hosea, N, Fanjul, A, Herrera, J, Chapman, J, Thalacker, F, et al. (2008). Demonstration of proof of mechanism and pharmacokinetics and pharmacodynamic relationship with 4′-cyano-biphenyl-4-sulfonic acid (6-amino-pyridin-2-yl)-amide (PF-915275), an inhibitor of 11-hydroxysteroid dehydrogenase type 1, in cynomolgus monkeys. J. Pharmacol. Exp. Ther. 324(1), 299–305.CrossRefGoogle Scholar
Courtney, R, Stewart, PM, Toh, M, Ndongo, M-N, Calle, RA, & Hirshberg, B. (2008). Modulation of 11{beta}-hydroxysteroid dehydrogenase (11{beta}HSD) activity biomarkers and pharmacokinetics of PF-00915275, a selective 11{beta}HSD1 inhibitor. J. Clin. Endocrinol. Metab. 93(2), 550–556.CrossRefGoogle Scholar
Scheen, AJ. (2008). CB1 receptor blockade and its impact on cardiometabolic risk factors: Overview of the RIO Programme with Rimonabant. J. Neuroendocrinol. 20(Suppl 1), 139–146.CrossRefGoogle ScholarPubMed
Subauste, A, & Burant, CF. (2003). DGAT: Novel therapeutic target for obesity and type 2 diabetes mellitus. Curr. Drug Targets Immune Endocr. Metabol. Disord. 3(4), 263–270.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×