Combination Therapy

This slide deck discusses using combination therapies in the treatment of Diabetes. It covers the importance of understanding individualized therapy and prescribing appropriate combination therapy for patients at high cardiovascular risk.

Screening and Monitoring of Prediabetes

AACE recommends that individuals who meet any of the clinical risk criteria noted below should be screened for prediabetes or type 2 diabetes (T2D)1.

Type 1 Diabetes Pathophysiology

Type 1 diabetes (T1D) is a chronic autoimmune disorder that occurs in genetically susceptible individuals and that may be precipitated by environmental factors. In a susceptible individual, the immune system is triggered to develop an autoimmune response against altered pancreatic beta cell antigens, or molecules in beta cells that resemble a viral protein.

Type 2 Diabetes Glucose Management Goals

Optimal management of type 2 diabetes requires treatment of the “ABCs” of diabetes: A1C, blood pressure, and cholesterol (ie, dyslipidemia). This web page provides the rationale and targets for glucose management; AACE guidelines for blood pressure and lipid control are summarized in Management of Common Comorbidities of Diabetes.

Management of Common Co-morbidities of Diabetes

As may be expected with a chronic disease that primarily affects middle-aged and older individuals, type 2 diabetes is usually complicated by other medical conditions.

Clinical Evidence for Glucose Control in the Inpatient Setting

Key Points

  • Epidemiologic studies show that glucose control in hospitals is woefully inadequate.

    • Approximately 30% of hospitalized patients have blood glucose values >180 mg/dL.

Mechanisms of Adverse Effects of Hyperglycemia in Acute Illness: A Review of the Basic Science

Key Points

  • Hyperglycemia and insulin regulation play both a direct and indirect role in the cellular mechanisms underlying inflammation and oxidative stress.

  • Free fatty acids generated by hyperglycemia and insulin deficiency also result in endothelial dysfunction and the generation of reactive oxygen species.

Financial Impact of Glycemic Control: Opportunities for Clinical and Financial Improvement

Key Points

  • Diabetes is an increasingly prevalent diagnosis among hospitalized patients.

    • Many patients have unrecognized diabetes.

  • Diabetes contributes to greater lengths of stay and increased costs among hospitalized patients.

  • Identifying and treating diabetes:

Management of Hyperglycemia in the Critical Care Setting

Key Points

  • Hyperglycemia is common in critically ill patients, both with and without diabetes.

  • Hyperglycemia is a predictor of adverse outcomes, including mortality.

Management of Hyperglycemia in the Noncritical Care Setting

Key Points

  • Hyperglycemia is associated with poor outcomes in noncritically ill patients.

  • Glycemic goals for noncritically ill patients

    • Premeal blood glucose: <140 mg/dL

    • Random blood glucose: <180 mg/dL

Diagnosis and Management of Hyperglycemic Crises: Diabetic Ketoacidosis and the Hyperglycemic Hyperosmolar State

Key Points

  • DKA and HHS are life-threatening emergencies.

  • Management involves

    • Attention to precipitating cause

    • Fluid and electrolyte management

    • Insulin therapy

    • Patient monitoring

    • Prevention of metabolic complications during recovery

Management of Inpatient Hyperglycemia in Special Populations

Key Points

  • Hyperglycemia is associated with adverse clinical outcomes in the hospital setting, both in critically ill and noncritically ill patients.

  • National organizations have promoted safe and achievable glucose targets for inpatients.

  • Special considerations are necessary for patients

Avoiding Hypoglycemia in the Hospital Setting

Key Points

  • Various patient- and provider-specific factors may increase the risk of inpatient hypoglycemia

  • Hypoglycemia is costly

    • - Patient level: increases risk of complications

    • - Institutional level: increases cost of care and may reduce reimbursement (Medicare “never” event)

Safety Concerns With Insulin Use in the Inpatient Setting: The Pharmacist’s Role

Key Points

  • Insulin is the most appropriate agent for the majority of hospitalized patients.

  • Insulin is a “high-alert medication.”

  • For effective and safe use of insulin, institutions need to consider

    • Standardized pharmacy operations

    • Education of nursing and support staff

Role of Nursing in the Continuum of Inpatient Diabetes Care

Key Points

  • Nurses are essential—and central—to successful implementation of protocols, order sets, glucose monitoring, and educational programs to support improved glycemic control.

Glycemic Control During Labor and Delivery

Key Points

  • The last 18 hours in utero have a significant impact on the infant’s metabolic responses after birth, even if maternal glucose control is adequate over the duration of gestation.

Successful Models of Implementation

Key Points

  • Hyperglycemia in the hospital affects quality of care, patient safety, length of stay, and cost; hence, addressing hyperglycemia in hospitalized patients can unite professionals in a common quest.

  • Models for implementation of improved control of hyperglycemia include:

Glucometrics: Assessing Quality in Inpatient Glycemic Management

Key Points

  • Glucometrics is a way to measure the success of inpatient glucose management. Getting timely and accurate metrics to frontline clinical teams, which can analyze the results and look for cause and effect, will transform performance improvement into optimal outcomes.

  • Glucometrics generally consists of 3 measures:

Strategies for Effective Discharge Planning for Hospitalized Patients With Diabetes

Key Points

  • Upon admission (or as soon thereafter as possible), every patient’s need for diabetes education should be assessed.

  • During hospital stay, all patients with diabetes should receive necessary training in diabetes knowledge and self-care skills.

Common Comorbidities and Complications of Prediabetes

Obesity is a neuroendocrine disease that is itself associated with numerous metabolic and biomechanical complications. It is generally defined as a body mass index (BMI) ≥30 kg/m2, especially in the presence of obesity-related complications. In the context of prediabetes, obesity (1-3):

Management of Prediabetes

Treatment Goals 
The primary goal of prediabetes management is to normalize glucose levels and prevent or delay progression to diabetes and associated microvascular complications (1,2). Management of common prediabetes comorbidities such as obesity, hypertension, dyslipidemia, cardiovascular disease, and chronic kidney disease is also essential.

The Burden of Diabetes


Diabetes affects 9.4% of the population of the United States, or approximately 30.3 million people. Of these, 7.2 million have not been diagnosed. Approximately 90% of all diabetes cases are type 2 diabetes.1

Type 1 Diabetes Diagnosis

Patients with type 1 diabetes (T1D) require exogenous insulin for survival and should be identified as soon as possible to avoid high morbidity due to a delay in insulin treatment.

Treatment of Type 1 Diabetes


  • Utilize intensive therapy aimed at near-normal BG and A1C levels
  • Prevent diabetic ketoacidosis and severe hypoglycemia
  • Achieve the highest quality of life compatible with the daily demands of diabetes management
  • In children, achieve nor

Clinical Presentation of Type 2 Diabetes Mellitus

Risk Factors

The risk factors for the development of both prediabetes and type 2 diabetes mellitus (T2DM) are as follows:1

Diagnosis of Type 2 Diabetes Mellitus

There is a continuum of risk for poor patient outcomes as glucose tolerance progresses from normal to overt type 2 diabetes.

Diabetes and Cancer

Epidemiologic data have demonstrated significant increases of various cancers in people with obesity and diabetes. Recently, concern has emerged that antihyperglycemic medications may also be associated with an increased prevalence of multiple cancers; however, available data are limited and conflicting.1,2

Team Approach to Type 2 Diabetes Management

Comprehensive care of patients with diabetes requires a team of healthcare professionals. Working with different healthcare providers allows the patient to learn in-depth information regarding their health and well-being. It also ensures that the patient’s needs are cared for and addressed.

Identification, Screening, and Diagnosis of Diabetes in Pregnancy

GDM Definition, Etiology, Risk Factors, and Pathophysiology


Nutrition and Obesity

1.1 Clinical Benefits of Weight Loss

Key Points
  • Obesity is a chronic relapsing progressive disease defined by abnormal or excessive adiposity that may impair health.
  • Improved ability to engage in activities of daily living such as improved mobility and reduction in symptoms of joint pain, bladder incontinence and obstructive sleep apnea.
  • Several metabolic benefits of weight loss i

1.2 Obesity Pathophysiology

Key Points
  • Obesity has a genetic basis as well as environmental and behavioral origins
  • Age contributes to a shift in balance between fat and muscle mass
  • Various negative feedback loops contribute to obesity
    • Increased caloric intake and reduced physical activity
      • Alters energy homeostasis, leading to a reduced metabol

1.3 Anthropometric Evaluation

Key Points
  • Evaluation of patients for obesity should include a complete history and physical examination
  • Body mass index (BMI) cutpoints vary with race and ethnicity
  • Waist circumference

1.4 Clinical Evaluation

Key Points
  • Clinical evaluation of obese patients should include a complete history and physical examination
  • Comorbidities and obesity complications should also be assessed
  • Treatment plans should be designed according to severity of comorbidities and complications as well as body mass index (BMI)

2.1 Epidemiology

Key Points
  • Obesity is increasing globally
    • Rates of obesity have risen dramatically in the U.S. over the past 4 decades
    • The increase in obesity is strongly associated with the increase in diabetes in the U.S. and worldwide
  • Obesity is costly

2.2 Metabolic Complications

Key Points
  • Obesity is associated with higher risks of prediabetes and type 2 diabetes (T2D)
  • Weight loss with lifestyle therapy, pharmacotherapy, or bariatric surgery
    • Reduces the risk of progression to T2D
    • Improves glycemic control in patients with T2D
    • Improves features of nonalcoholic fatty liver disease (NAFLD) and n

2.3 Cardiovascular Complications

Key Points
  • Obesity is associated with increased cardiovascular risk
  • Weight loss by means of lifestyle therapy, pharmacotherapy, or bariatric surgery positively affects cardiovascular risk markers

2.4 Organ-Specific, Hormonal, and Biomechanical Complications

Key Points
  • Numerous organ-specific and biomechanical complications accompany obesity
  • Weight loss ameliorates all of these conditions

2.5 Psychological Complications (Coming Soon)

Key Points
  • Depression, anxiety, eating disorders, and other psychological conditions frequently are associated with obesity
  • Weight loss may positively affect the psychological complications of obesity.

3.1 Lifestyle Intervention

Key Points
  • Lifestyle interventions effectively prevent physical and metabolic complications of obesity
    • Lifestyle alone is less effective in populations with more severe obesity
  • Weight loss with lifestyle change is difficult to maintain
    • Behavioral support may need to be intensified to assist with weight loss and ma

3.2 When to Initiate Pharmacotherapy

Key Points
  • Weight-loss medications should be considered when obesity-related complications can be ameliorated by weight loss.
  • Pharmacotherapy should always be combined with lifestyle therapy, never used alone.

3.3 Weight Loss Medications

Key Points
  • Older obesity pharmacotherapies are limited by tolerability and dependence issues and are approved only for short-term use (≤12 weeks).
  • Newer weight loss agents are typically better tolerated, have better safety profiles, and are approved for chronic weight management including weight maintenance.
  • Pharmacotherapy for overweight an

3.4 Bariatric Surgery

Key Points
  • Four weight-loss surgical options are available
    • Laparoscopic adjustable gastric band (LAGB)
    • Laparscopic sleeve gastrectomy (LSG)
    • Biliopancreatic diversion with or without duodenal switch (BPD-DS) and with or without LSG (staged BPD)
    • Roux-en-Y gastric bypass (RYGB)
  • BPD-DS and RYGB yi

Lipids and CV Health

Managing Lipids in Diabetes - Landmark Trials of Intensive Diabetes Control and Cardiovascular Complications

What impact does intensive blood glucose control have on CV complications in patients with diabetes? What are the major findings of CV outcome trials conducted the past 10 years? Does intensive glucose control improve CV mortality? What are important considerations for future studies?

Managing Lipids in Diabetes - Cardiovascular Outcomes Trials in Type 2 Diabetes

What are the main objectives of the cardiovascular outcomes trials (CVOT) for type 2 diabetes (T2D) therapeutics? Over the past 7 years, what have the outcomes of major CVOTs for T2D therapeutics shown? Which drug classes have demonstrated the greatest cardiovascular benefits? How have diabetes guidelines changed in response to results of CVOT trials?

Risk Assessment & Goals - Assessing CVD Risk: Risk Calculators

How is ASCVD risk assessed? What are the benefits and disadvantages of the various available risk assessment tools? Is metabolic syndrome a stronger predictor of CV risk compared to CV risk scoring tools? How do emerging risk markers further refine risk stratification?

Risk Assessment & Goals - The Cholesterol Hypothesis to the Cholesterol Principle: Genetic, Epidemiologic, and Clinical Trials Proving Causality

The Cholesterol Hypothesis, also known as the Lipid Hypothesis, postulates a direct link between blood cholesterol levels and CHD. Studies show a higher and earlier occurrence of heart disease in patients with higher blood lipid levels. Strategies to decrease plasma lipid levels (primarily LDL - C) reduces CHD risk at the patient and population level. Although other CHD risk factors exist, the causal role of lipid accumulation in CHD pathogenesis has been shown in clinical, epidemiologic, and genetic analyses. Based on the strength of available evidence, is it time to rename the “Cholesterol Hypothesis” the “Cholesterol Principle”?

Risk Assessment & Goals - Triglyceride-Rich Lipoproteins

What are the types and key features of triglyceride - rich lipoproteins (T G RLs)? What are the endogenous and exogenous metabolic pathways of T G RLs ? What is the role of polymorphisms in metabolic abnormalities of triglycerides? What role do T G RLs play in atherosclerotic cardiovascular disease (ASCVD)?

Treatment Strategies - Niacin Nicotinic Acid (Vitamin B3)

What is nico7nic acid (niacin)? What are the recognized side effects of niacin? What are the key results from clinical and imaging trials of niacin treatment? How did results from “historical” trials differ from results of the more “recent” AIM - HIGH and HPS2 - THRIVE RCTs, and how did trial designs differ?

Treatment Strategies - Statins

What is the role of statin therapy in the management of dyslipidemia and prevention of CVD? What are starting statin doses, dosage ranges, metabolic effects, and main considerations? How should statin treatment be monitored? What is the major evidence supporting the use of statin therapy?

Treatment Strategies - Merits of Targeting LDL - C, Triglycerides, HDL - C, and Non - HDL - C, and Addressing Residual Risk

What risk factors contribute to a patient's total risk profile for cardiometabolic disease, including residual CAD risk? How does targeting HDL - C vs HDL - P affect risk? What are the merits of targeting (reducing) TG and how does the setting of high cholesterol contribute to risk associated with high TGs? What are the benefits of lowering LDL - C, non - HDL - C, Apo B, and LDL - P? How low should LDL - C lowering go?

Treatment Strategies - Proprotein Convertase Sub1lisin/ Kexin Type 9 (PCSK9) Inhibitors

What are proprotein convertase subtilisin/ kexin type 9 ( PCSK9) inhibitors and how do they work? Which patients are candidates for PCSK9 inhibitor therapy? What is the expected response to PCSK9 inhibitor therapy?

Treatment Strategies - Novel New Therapeutic Classes for Atherosclerotic Cardiovascular Disease

What have recent studies shown regarding residual CV risk in patients on statins? What new agents are available to address residual risk? What are the mechanisms of action of these therapeutics, and what patient populations do they benefit? What are current AACE recommendations for the use of novel new therapeutic agents for ASCVD?

Treatment Strategies - Assessment and Treatment of Hypertriglyceridemia

What is the risk burden of hypertriglyceridemia? What is the clinical and gene7c evidence for the associa7on between elevated TG and atherosclerosis? What are the evidence - based guideline recommenda7ons for managing pa7ents with hypertriglyceridemia? What TG - lowering agents are available, and what are their an7 - atherosclero7c and an7 - inflammatory proper7es?

Treatment Strategies - Dyslipidemia Management

What are the causes of dyslipidemia? What are current lipid treatment goals? What treatments are available for dyslipidemia? How should treatment be monitored?

Treatment Strategies - Fibrates

What is the role of fibrates in the treatment of dyslipidemia? What key studies have demonstrated significant clinical benefit with combination therapy (statins + fibrates)? What are the current AACE treatment guidelines regarding the use of fibrates for dyslipidemia management? What specific populations benefit from fibrate therapy?

Treatment Strategies - Omega - 3 Fatty Acids

What are omega - 3 fatty acids/fish oil and how do they fit into treatment for dyslipidemia? What are the recommendations and considerations for treatment with omega - 3 fatty acids/fish oil?

Treatment Strategies - Dietary Strategies for Improving Cardiovascular Health

What dietary factors increase the risk of CVD? What is the place of nutrition in reducing the risk of CVD and improving cardiovascular health in patients with dyslipidemia? How do different nutrients contribute to improving CVD health?

ACSVD Risk in Special Situations - Familial Chylomicronemia Syndrome (FCS)

What is familial chylomicronemia syndrome (FCS) and how does it differ from other types of severe HTG? What is the pathophysiology of severe HTG and FCS? What are the adverse consequences of severe HTG (with or without FCS) and what is their pathophysiology? How should FCS be diagnosed? How should FCS be management?

Bone and Parathyroid

Rare Metabolic Bone Diseases

Fibrous dysplasia (FD), Osteogenesis imperfecta (OI), also known as brittle bone disease, and Hypophosphatasia are rare genetic bone disorders.View the slide library to learn about

Postmeopausal Osteoporosis

Postmenopausal osteoporosis is preventable and treatable, but only a small proportion of women at increased risk for fracture are evaluated and treated. View the slide library for information about 

  • Diagnosis
  • Screening
  • Treatment
  • Combination therapy

Primary Hyperparathyroidism

In the United States, primary hyperparathyroidism is the most common cause of hypercalcemia encountered in ambulatory care. Through our slide library, learn about

  • Epidemiology
  • Diagnosis
  • Clinical presentation
  • Surgical treatment
  • Medical management

Vitamin D Deficiency

Vitamin D deficiency results in abnormalities in calcium, phosphorous, and bone metabolism. View the slide library for information about this deficiency, including

  • Definitions
  • Screening
  • Diagnosis
  • Treatment
  • Prevention

Pagets Disease of the Bone

Paget’s disease is the second most common bone remodeling disease after osteoporosis, occurring in 1%-2% of white adults older than 55. View our slide library for information about this bone disorder, including

  • Possible Causes
  • Clinical Presentation
  • Diagnosis
  • Treatment
  • Follow Up Assessment

Male Osteoporosis

More than 8 million of the 44 million Americans who have either osteoporosis or low bone mineral density (BMD) are men. Through our slide library, learn about:

  • Epidemiology of Osteoporosis in Men
  • Clinical Presentation
  • Diagnosis
  • Lifestyle recommendations
  • Medical management

Familial Hypocalciuric Hypercalcemia and Benefits of Genetic Confirmation: A Case Report and Review

Respina Jalilian, Mehran Jalilzadeh Binazar and Lubna Mirza

AACE Clinical Case Reports 

Nov 2017, Vol. 3, No. 4 (Autumn 2017) pp. e361-e363