Management of diabetes across the course of disease: minimizing obesity-associated complications

Figures & data

Figure 1 Distribution of body mass index (BMI) values for patients with type 1 or type 2 diabetes mellitus in the Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes.

Note: Copyright © 2007. John Wiley and Sons. Reproduced with permission from Bays HE, Chapman RH, Grandy S. The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys. Int J Clin Pract. 2007;61(5): 737–747.⁴

Table 1 Oral antihyperglycemic medications available in the USA

Class	Medication
Biguanides	Liquid metformina (Riomet^®) Metforminb (Glucophage^®) Metformin extended-releaseb (Glucophage XR^®, Fortamet^®, Glumetza^®)
Thiazolidinediones	Pioglitazone (Actos^®) Rosiglitazone (Avandia^®)c
Alpha-glucosidase inhibitors	Acarbose (Precose^®) Miglitol (Glyset^®)
Insulin secretagogues	Sulfonylureas – Glimepirideb (Amaryl^®) – Glipizideb (Glucotrol^®) – Glipizide extended-release (Glucotrol XL^®) – Glyburideb (Micronase^®, Diabeta^®) – Micronized glyburide (Glynase^®) Nonsulfonylurea meglitinides – Repaglinide (Prandin^®) D-phenylalanine derivatives – Nateglinide (Starlix^®)
DPP-4 inhibitors	Sitagliptin (Januvia^®) Saxagliptin (Onglyza™)
Bile acid sequestrant	Colesevelam (Welchol^®)
Fixed combinations	Metformin and glipizide (Metaglip^®) Metformin and glyburide (Glucovance^®) Metformin and pioglitazone (ACTOplus met^®) Pioglitazone and glimepiride (Duetact^®) Rosiglitazone and glimepiride (Avandaryl^®)c Rosiglitazone and metformin (Avandamet^®)c Sitagliptin and metformin (Janumet^®) Repaglinide and metformin (PrandiMet^®)

a Notes: Liquid formulation for patients unable to swallow pills;

b Available as a generic medication;

c On September 23, 2010, the Food and Drug Administration (FDA) announced regulatory actions with respect to products containing rosiglitazone. The FDA is requiring GlaxoSmithKline (GSK) to implement restrictions on the use of these products through a program to assure their safe use and additional safety labeling changes in response to the agency’s review of data that suggest an elevated risk of cardiovascular events. Adapted with permission from Joslin Clinical Guideline for Pharmacological Management of Type 2 Diabetes, copyright © 2009 (updated 11/2010) by Joslin Diabetes Center (www.joslin.org). All rights reserved.³⁴

Abbreviation: DPP-4, dipeptidyl peptidase-IV.

Table 2 Injectable diabetes medications available in the USA: (A) insulins and (B) incretin mimetics and noninsulin synthetic analogs

A) Insulin type	Product	Onseta	Peaka	Durationa
Rapid acting
Insulin aspart analog	NovoLog^®	10–30 min	30 min–3 h	3–5 h
Insulin glulisine analog	Apidra^®	10–30 min	30 min–3 h	3–5 h
Insulin lispro analog	Humalog^®	10–30 min	30 min–3 h	3–5 h
Short acting
Human regular insulin	Humulin R^® Novolin R^®	30–60 min	2–5 h	Up to 12 hb
Intermediate acting
Human NPH insulin	Humulin N^® Novolin N^®	90 min–4 h	4–12 h	Up to 24 hc
Long acting
Insulin detemir	Levemir^®	45 min–4 h	Minimal peak	Up to 24 hd
Insulin glargine	Lantus^®	45 min–4 h	Minimal peak	Up to 24 hd
Premixed insulin combinations
50% NPH; 50% regular	Humulin 50/50^®
70% NPH; 30% regular	Humulin 70/30^®
70% NPH; 30% regular	Novolin 70/30^®
50% lispro protamine suspension, 50% lispro	Humalog Mix 50/50^®
50% aspart protamine suspension, 50% aspart	Novolog Mix 50/50^®
75% lispro protamine suspension, 25% lispro	Humalog Mix 75/25^®
70% aspart protamine suspension, 30% aspart	NovoLog Mix 70/30^®
B) Incretin mimetics and noninsulin synthetic analogs	Mechanism of action	Type of diabetes	# of injections/day
Exenatide (Byetta^®)	Incretin mimetic that enhances glucose-dependent insulin secretion and several other antihyperglycemic actions of incretins.	2	2
Liraglutide (Victoza^®)	A GLP-1 receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control.	2	1 (independent of meals)
Pramlintide (Symlin^®)	Synthetic analog of human amylin, a naturally occurring hormone made in the β-cells, which slows gastric emptying, suppresses glucagon secretion, and regulates food intake. A significant reduction in insulin dose may be required when insulin is used in conjunction with pramlintide.	1 and 2	1–4 (with meals)

a Notes: The onset, peak, and duration of any insulin type depends on many factors. Patients may experience variations in timing and/or intensity of insulin activity due to dose, site of injection, temperature of the insulin, level of physical activity, in addition to other factors;

b Usual clinical relevance can be less than 12 hours;

c Usual clinical relevance can be less than 24 hours. Often requires twice-daily dosing.

d Individual response may require twice-daily dosing. Adapted with permission from Joslin Clinical Guideline for Pharmacological Management of Type 2 Diabetes, copyright © 2009 (updated 11/2010) by Joslin Diabetes Center (www.joslin.org). All rights reserved.³⁴

Abbreviations: GLP-1, glucagon-like peptide-1; h, hours; min, minutes; NPH, neutral protamine Hagedorn; #, number.

Figure 2 Differences (with 95% confidence intervals [CI]) between long-acting analogs and neutral protamine Hagedorn insulin in the effects on body mass index at endpoint in clinical trials of patients with type 1 or type 2 diabetes mellitus.

Notes: Used with permission from Diabetes Research and Clinical Practice, Vol 81, Pages 184–189, M Monami, N Marchionni, E Mannucci. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis. © Copyright Elsevier 2008.⁷⁹

Table 3 Pharmacotherapy for obesity in the USA

Drug	Mechanism of action	Cardiovascular effects	Weight loss*	Status
Fenfluramine/phentermine resin	5HT-releasing agent and reuptake inhibitor/norepinephrine-releasing agent	Cardiac valvulopathy and pulmonary hypertension	11.0% (34 weeks)	Fenfluramine withdrawn in 1997; phentermine still available
Fenfluramine, dexfenfluramine	5HT-releasing agent and reuptake inhibitors	Cardiac valvulopathy and pulmonary hypertension	3.0%	Both withdrawn in 1997
Sibutramine	Norepinephrine/serotonin reuptake inhibitor; induces satiety/increases energy expenditure	BP and pulse elevations, MI, and stroke risk	3.7%–5.0%	Withdrawn in 2010
Phentermine resin, diethylpropion	Norepinephrine releasing agents	BP and pulse elevations	8.1% (36 weeks)	Approved in 1960s for short-term use
Mazindol	Norepinephrine reuptake inhibitor	BP and pulse elevations	2%–10% (12 weeks)	Discontinued in 1999
Phenylpropanolamine	A1 adrenergic agonist	Increased risk of hemorrhagic stroke	0%–2.0% (12 weeks)	Withdrawn from OTC market in 2000
Orlistat	Pancreatic and gastric lipase inhibitor	None known	2.9%–3.4%	FDA approved in 1999 for long-term use
Rimonabant	Endocannabinoid receptor type 1 blocker	NA	5.0%	Not approved 2007, psychiatric side effects cited
Topiramate/phentermine	GABA receptor modulation	BP and pulse elevations	8.6%	Not approved in 2010, cardiovascular effects and teratogenicity cited
Bupropion/naltrexone	Dopamine, norepinephrine reuptake inhibitor/opioid antagonists	BP elevation	4.8%	Not approved in 2010, FDA requesting preapproval long-term cardiovascular study
Lorcaserin	5HT2c receptor agonist	Possible valvulopathy	3.6%	Not approved in 2010, breast tumors in animals cited
Bupropion/zonisamide	Dopamine norepinephrine reuptake inhibitor/sodium channel modulator	BP elevation	6.1%	Phase IIB/II
Pramlintide/metreleptin	Incretin and adipose tissue hormone with satiety signal in hypothalamus	NA	9.2% (28 weeks)	Phase IIB
Liraglutide	GLP-1 agonist	NA	4.5% (20 weeks)	Phase IIB/III

* Notes: Mean weight loss in excess of placebo as percentage initial body weight across 1 year, unless otherwise specified. Used with permission from Apovian and Gokce.⁸⁹

Abbreviations: BP, blood pressure; MI, myocardial infarction; OTC, over the counter; GLP-1, glucagon-like peptide-1; FDA, Food and Drug Administration; NA, not available; GABA, gamma-aminobutyric acid; 5HT, 5-hydroxytryptamine.

Figure 3 Commonly used bariatric surgery procedures.

Notes: From Weight Control Information Network and National Institute of Diabetes and Digestive and Kidney Diseases.¹¹⁶ Image used with permission from Walter Pories, MD, FACS. ©Copyright University of North Carolina.

Bays HE Chapman RH Grandy S The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys Int J Clin Pract 2007 61 5 737 747 17493087

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Joslin Diabetes Center and Joslin Clinic Clinical Guideline for Pharmacological Management of Type 2 Diabetes January 9 2009 updated November, 2010. Available from: http://www.joslin.org/bin_from_cms/Pharma_guideline_11._10.pdf Accessed July 28, 2011

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Monami M Marchionni N Mannucci E Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis Diabetes Res Clin Pract 2008 81 2 184 189 18495286

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Apovian CM Gokce N Clinician update: obesity and cardiovascular disease Circulation 2011

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Weight Control Information Network and National Institute of Diabetes and Digestive and Kidney Diseases Bariatric surgery for severe obesity. [Page on the Internet.] 3 2009 Available from: http://win.niddk.nih.gov/publications/gastric.htm#whataresurg Accessed July 28, 2011

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