As the word has been celebrating innovations and technological achievements during
the last few decades, there has also been a noticeable increase in various non-communicable
diseases, attributed, at least in part, to modernization and globalization [
1
,
2
]. In an era of increased sedentary lifestyle and unhealthy diet, obesity has been
spreading steadily [
[3]
]. Initially, this modern era pandemic of metabolic diseases due to obesity remained,
and to a large extent still remains, largely overlooked, due to the slower pace and
longer periods needed for the development of comorbidities [
4
,
5
], as compared for example to COVID-19, Ebola, influenza and other epidemics of communicable
diseases [
[6]
]. Overweight and obesity affect one third to two thirds of children and adults in
the US, Europe and other regions [
7
,
8
], and the numbers are still rising. Approximately 80 % of patients with excess weight
have metabolically unhealthy obesity, and the numbers of those afflicted by obesity
induced comorbidities are definitively higher if one also considers individuals who
have a normal body mass index (BMI), but central distribution of fat and an unhealthy
metabolic profile, and thus are at a high risk of complications [
9
,
10
]. This is the time to act to address the obesity epidemic by preventing and/or treating
excess weight, and thus reducing the associated morbidity and mortality [
[11]
].Abbreviations:
Food and Drug Administration (FDA), Tirzepatide (TZP), Glucose-dependent insulinotropic polypeptide (GIP), Glucagon-like peptide 1 (GLP-1), Type 2 diabetes mellitus (T2D), Hemoglobin A1c (HbA1c), Body mass index (BMI), Sodium-glucose Cotransporter-2 (SGLT2)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Metabolism - Clinical and ExperimentalAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- How some effects of modernization fuel non-communicable diseases in Africa.(Available from)https://www.afro.who.int/news/how-some-effects-modernization-fuel-noncommunicable-diseases-africa([accessed February 2023])Date: 2011
- What is driving global obesity trends? Globalization or "modernization"?.Glob Health. 2019; 15: 32
- Prevalence of obesity | World Obesity Federation.(Available from) ([accessed February 2023])
- Obesity as a risk factor for Alzheimer's disease: weighing the evidence: obesity as a risk factor for Alzheimer's disease.Obes Rev. 2018; 19: 269-280
- Metabolic complications of obesity.Best Pract Res Clin Endocrinol Metab. 2013; 27: 179-193
- Obesity: another ongoing pandemic.J Gastroenterol Hepatol. 2021; 6: 411
- WHO European regional obesity report 2022.World Health Organization. Regional Office for Europe, 2022
- WHO report highlights the dangers of obesity.(Available from) ([accessed February 2023])
- Insulin resistance and vascular dysfunction in nondiabetic Asian Indians.J Clin Endocrinol Metab. 2004; 89: 3965-3972
- Metabolic health and weight: understanding metabolically unhealthy normal weight or metabolically healthy obese patients.Metab Clin Exp. 2016; 65: 73-80
- Weight loss and improvement in comorbidity: differences at 5%, 10%, 15%, and over.Curr Obes Rep. 2017; 6: 187-194
- Novel noninvasive approaches to the treatment of obesity: from pharmacotherapy to gene therapy.Endocr Rev. 2022; 43: 507-557
- Pharmacotherapy of obesity: an update on the available medications and drugs under investigation.eClinicalMedicine. 2023; (Accepted)
- Positional cloning of the mouse obese gene and its human homologue.Nature. 1994; 372 (London): 425-432
- Leptin in human physiology and pathophysiology.Am J Physiol Endocrinol. 2011; 301: E567-E584
- Leptin in human physiology and therapeutics.Front Neuroendocrinol. 2010; 31: 377-393
- The role of leptin in human obesity and disease: a review of current evidence.Ann Intern Med. 1999; 130: 671-680
- The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men.J Clin Investig. 2003; 111: 1409-1421
- Narrative review: the role of leptin in human physiology: emerging clinical applications.Ann Intern Med. 2010; 152: 93-100
- Mechanisms of disease: the role of gastrointestinal hormones in appetite and obesity.Nat Clin Pract Gastroenterol Hepatol. 2008; 5: 268-277
- Peripheral mechanisms in appetite regulation.Gastroenterology. 2015; 148 (New York, NY 1943): 1219-1233
- Will medications that mimic gut hormones or target their receptors eventually replace bariatric surgery?.Metab Clin Exp. 2019; 100153960
- Peptide YY levels are elevated after gastric bypass surgery.Obesity. 2006; 14 (Silver Spring, Md): 194-198
- The function of gastrointestinal hormones in obesity—implications for the regulation of energy intake.Nutrients. 2021; 13: 1839
- Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer's and Parkinson's disease models.Neuropharmacology. 2018; 136: 251-259
- GLP1 agonists beyond glycemic control—redefining their role.Int J Diabetes Dev Ctries. 2020; 40: 461-463
- Leptin in leanness and obesity: JACC state-of-the-art review.J Clin Investig. 2021; 77: 745-760
- Anti-obesity drugs: past, present and future.Dis Model Mech. 2012; 5: 621-626
- Food and drug administration's obesity drug guidance document a short history.Circulation. 2012; 125 (New York, NY): 2156-2164
- Pharmacological management of obesity: an endocrine society clinical practice guideline.J Clin Endocrinol Metab. 2015; 100: 342-362
- Once-weekly semaglutide in adults with overweight or obesity.N Engl J Med. 2021; 384: 989-1002
- American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity.Endocr Pract. 2016; 22: 1-203
- An updated approach to antiobesity pharmacotherapy: moving beyond the 5% weight loss goal.JES. 2023; 7bvac195
- Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial.Lancet Diabetes Endocrinol. 2016; 4: 913-921
- Intensive weight loss intervention and cancer risk in adults with type 2 diabetes: analysis of the look AHEAD randomized clinical trial.Obesity. 2020; 28 (Silver Spring, Md): 1678-1686
- Association between weight loss and serum biomarkers with risk of incident cancer in the longitudinal assessment of bariatric surgery cohort.Surg Obes Relat Dis. 2020; 16: 1086-1094
- Dual gut hormone receptor agonists for diabetes and obesity.J Clin Invest. 2023; 133
- Structural determinants of dual incretin receptor agonism by tirzepatide.Proc Natl Acad Sci. 2022; 119e2116506119-e
- Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading gylcaemic control and body weight reduction.Cardiovasc Diabetol. 2022; 21: 169
- Mounjaro™ (tirzepatide) injection.(Available from) ([accessed February 2023])
- How may GIP enhance the therapeutic efficacy of GLP-1?.Trends Endocrinol Metab. 2020; 31: 410-421
- Chapter 15 glucose-dependent insulinotropic polypeptide (Gastric Inhibitory Polypeptide; GIP).in: Vitam Horm. 80. Elsevier Science & Technology, 2009: 409-471
- The influence of Glucose-dependent Insulinotropic Polypeptide (GIP) on human adipose tissue and fat metabolism: implications for obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).Peptides. 2020; 125 (New York, NY:1980)170208
- Biology of incretins: GLP-1 and GIP.Gastroenterology. 2007; 132 (New York, NY 1943): 2131-2157
- Short-term administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: a randomized, placebo-controlled, crossover study.Metab Clin Exp. 2016; 65: 945-953
- Longer-term liraglutide administration at the highest dose approved for obesity increases reward-related orbitofrontal cortex activations to food cues: implications for plateauing weight loss in response to anti-obesity therapies.Diabetes Obes Metab. 2019; 21: 2459-2464
- GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial.Diabetologia. 2016; 59: 954-965
- Semaglutide lowers body weight in rodents via distributed neural pathways.JCI Insight. 2020; 5
- Effects of peripheral administration of synthetic human glucose-dependent insulinotropic peptide (GIP) on energy expenditure and subjective appetite sensations in healthy normal weight subjects and obese patients with type 2 diabetes.Clin Endocrinol (Oxf). 2009; 71: 195-201
- Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study.Diabetologia. 2019; 62: 665-675
- Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial.Lancet. 2021; 398 (British edition): 143-155
- Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes.N Engl J Med. 2021; 385: 503-515
- Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial.Lancet. 2021; 398 (British edition): 583-598
- Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial.Lancet. 2021; 398 (British edition): 1811-1824
- Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial.JAMA. 2022; 327: 534-545
- Efficacy and safety of tirzepatide as novel treatment for type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials.Diabetes Metab Syndr Clin Res Rev. 2022; 16102640
- SURMOUNT-1 investigators. Tirzepatide once weekly for the treatment of obesity.N Engl J Med. 2022; 387: 205-216
- What is weight loss after bariatric surgery expressed in percentage total weight loss (%TWL)?A systematic review.Obes Surg. 2021; 31: 3833-3847
- FDA grants fast track designation to Tirzepatide for obesity, associated comorbidities pharmacy times.(Available from) ([accessed February 2023])
- Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial.Lancet Diabetes Endocrinol. 2022; 10: 393-406
- A study of tirzepatide (LY3298176) on the reduction on morbidity and mortality in adults with obesity.(Available from) ([accessed February 2023])
- A study of tirzepatide (LY3298176) compared with dulaglutide on major cardiovascular events in participants with type 2 diabetes (SURPASS-CVOT).
- Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.Nat Med. 2022; 28: 591-598
- Updated meta-analysis assessing the cardiovascular efficacy of tirzepatide.Am J Card. 2022; 181: 139-140
- Adverse events related to tirzepatide.J Endocr Soc. 2023; https://doi.org/10.1210/jendso/bvad016
- Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: a network meta-analysis of randomized clinical trials.Obes Rev. 2022; e13543-e
- Clinical recommendations to manage gastrointestinal adverse events in patients treated with GLP-1 receptor agonists: a multidisciplinary expert consensus.J Clin Med. 2022; 12: 145
- Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice.Postgrad Med. 2022; 134: 14-19
- Tirzepatide for the treatment of obesity: rationale and design of the SURMOUNT clinical development program.Obesity. 2023; 31 (Silver Spring, Md): 96-110
- Anti-obesity drug discovery: advances and challenges.Nat Rev Drug Discov. 2022; 21: 201-223
- Targeting energy expenditure—drugs for obesity treatment.Pharmaceuticals. 2021; 14 (Basel, Switzerland): 435
- A study of tirzepatide (LY3298176) in participants with obesity or overweight.([accessed February 2023])
- Efficacy of semaglutide in a subcutaneous and an oral formulation.Front Endocrinol. 2021; 12 (Lausanne)645617
- Research study to investigate how well Semaglutide tablets taken once daily work in people who Are overweight or living with obesity (OASIS 1).(Available from) ([accessed February 2023])
- Closing obesity care gaps and achieving health equity for people living with obesity.Eur J Intern Med. 2021; 91: 1-2
- Evidence of a gap in understanding obesity among physicians.Obes Sci Pract. 2018; 4: 46-51
- Clinical perspectives on obesity treatment: challenges, gaps, and promising opportunities.NAM Perspect. 2018; https://doi.org/10.31478/201809b
Article info
Publication history
Published online: March 02, 2023
Accepted:
February 27,
2023
Received:
February 26,
2023
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.