Diabetes Drug Notes

Diabetes is becoming more common in both older and younger generations and in keeping with this escalation in cases, there are an ever increasing number of drugs and drug classes that are suitable to treat hyperglycaemia. In a unique blend of diabetes practice, clinical pharmacology, and cardiovascular medicine, Diabetes Drug Notes describes the principles of clinical pharmacology with regards to diabetes prescribing. Each drug class for the treatment of diabetes is covered in detail, along with the effect on the cardiovascular and renal systems caused by each drug. Building upon the success of their “Drug Notes” series for Practical Diabetes and their “Drugs for Diabetes” series in the British Journal of Cardiology, the team of experts focuses on the glycaemic management of type 1 and type 2 diabetes, with other effects of antidiabetic drugs covered as well.

Diabetes Drug Notes also includes:

• Comprehensive and up-to-date coverage of the drugs for the glycaemic management of patients with type 1 or type 2 diabetes
• Expert reflection on prescribing considerations for special groups, as well as common pitfalls in prescribing
• Detailed case histories to illustrate relevant information
• Summaries of recent guidelines related to diabetic intervention

Diabetes Drug Notes is a user-friendly guide for a general diabetes medical, nursing, and pharmacology readership, as well as those who support them.

Prof. Miles Fisher is a former Consultant Physician, Department of Diabetes, Endocrinology and Clinical Pharmacology, Glasgow Royal Infirmary, and an Honorary Professor at the University of Glasgow, UK.

Prof. Gerard McKay is a Consultant Physician, Department of Diabetes, Endocrinology and Clinical Pharmacology, Glasgow Royal Infirmary, an Honorary Clinical Associate Professor, University of Glasgow, as well as a Visiting Professor at the University of Strathclyde, UK.

Dr Andrea Llano is a Consultant Physician, Department of Diabetes, Endocrinology and Clinical Pharmacology, Glasgow Royal Infirmary, and an Honorary Clinical Lecturer, University of Glasow, UK.

Contents

Foreword xx

Preface xxi

Editors and Contributors xxii

Introduction 1

1 Clinical Pharmacology of Antidiabetic Drugs 2

Andrea Llano, Gerry McKay, and Ken Paterson

Introduction 2

Clinical Pharmacology 3

Drug Development and Clinical Trials 7

Drug Licensing of Antidiabetic Drugs 12

Development and Licensing of Insulin 14

Pharmacovigilance 19

Pharmacoeconomics 21

Future Developments in Diabetes Clinical Pharmacology 26

2 Metformin 30

Joseph Timmons and James Boyle

Introduction 30

Pharmacology 32

Glycaemic Efficacy 36

Safety and Side Effects 37

Outcome Trials 38

Metformin in Type 1 Diabetes 45

Place of Metformin in Current and Future Practice 46

3 Sulfonylureas and Meglitinides 49

Joseph Timmons and James Boyle

Introduction 49

Pharmacology 51

Glycaemic Efficacy 53

Safety and Side Effects 55

Outcome Trials 56

Meglitinides 61

Place of Sulfonylureas and Meglitinides in Current and Future Practice 65

4 DPP-4 Inhibitors 67

Sharon Mackin and Gemma Currie

Introduction 67

Pharmacology 68

Glycaemic Efficacy 75

Safety and Side Effects 79

Outcome Trials 82

The Place of DPP-4 Inhibitors in Current and Future Practice 91

5 SGLT2 Inhibitors 95

Miles Fisher, Andrea Llano, and Gerry McKay

Introduction 96

Pharmacology 96

Glycaemic Efficacy 100

Side Effects and Safety 103

Outcome Trials 105

SGLT2 Inhibitors in Type 1 Diabetes 119

Use of SGLT2 Inhibitors in Other Diseases 123

Place of SGLT2 Inhibitors in Current and Future Practice 124

6 GLP-1 Receptor Agonists 130

Catherine Russell and John Petrie

Introduction 130

Pharmacology 131

Glycaemic Efficacy and Effect on Weight 137

Side Effects and Safety 142

Outcome Trials 143

Use of GLP-1 Receptor Agonists in Other Diseases 153

Place of GLP-1 Receptor Agonists in Current and Future Practice 155

7 Animal and Human Insulins 161

Ken Paterson

Introduction 161

Production and Pharmacokinetic Modifications 165

Limitations of Older Insulins 170

Intensified Insulin Therapy 173

Place of Human Insulin in Current and Future Therapy 176

8 Short-acting Insulin Analogues 179

Kate Hughes and Gerry McKay

Introduction 179

Factors Affecting Absorption and Metabolism of Short-acting Insulin 180

Manufacturing Insulin Analogues 180

Short-acting Insulin Analogues 182

Second-generation Ultrafast-acting Insulin Analogues 186

Other Attempts to Improve Insulin Absorption and Inhaled Insulin 189

Place of Short-acting Insulin Analogues in Current and Future Practice 190

9 Long-acting Insulin Analogues 194

Robert Lindsay

Introduction 195

Development of Long-acting Insulin Analogues 196

Long-acting Insulin Analogues 197

Meta-analysis of Glycaemic Efficacy of Long-acting Insulin Analogues 207

Safety of Long-acting Insulin Analogues 209

The Place of Long-acting Insulin Analogues in Current and Future
Practice 209

10 Devices 214

David Carty

Introduction 214

Insulin Pens 215

Insulin Pumps 215

Self-monitoring of Blood Glucose 218

Linkage of Continuous Glucose Monitoring to Insulin Pumps 223

Guidelines on the Use of Devices 225

Place of Devices in Current and Future Practice 227

11 Acarbose and Alpha Glucosidase Inhibitors 229

Miles Fisher

Introduction 229

Pharmacology 230

Glycaemic Efficacy 231

Safety and Side Effects 232

Outcome Trials 232

Place of Alpha Glucosidase Inhibitors in Current and Future Practice 237

12 Glitazones and Glitazars 239

Miles Fisher

Introduction 239

Pharmacology 240

Glycaemic Efficacy 241

Safety and Side Effects 242

Outcome Trials 245

Glitazars 252

Place of Glitazones and in Current and Future Practice 253

13 Other Antidiabetic Drugs 257

Maroria Oroko, Andrea Llano, and Miles Fisher

Introduction 257

Pramlintide 258

Colesevelam 260

Bromocriptine 262

Hydroxychloroquine 264

Antiobesity Drugs 265

Place of Other Drugs in Current and Future Practice 270

14 Future Antidiabetic Drugs 274

Emma Johns and Miles Fisher

Introduction 274

Dual and Triple Agonists 275

Imeglimin 288

Place of New Antidiabetic Drugs in Future Practice 291

15 Guidelines on Antidiabetic Drugs 294

Miles Fisher and Russell Drummond

Introduction 295

Guidelines on the Use of Antidiabetic Drugs in Type 2 Diabetes 298

Guidelines on the Management of Type 1 Diabetes 308

Special Patient Groups 311

Place of Guidelines in Current and Future Practice 318

16 Prescribing Antidiabetic Drugs 322

Andrea Llano, Gerry McKay, Frances McManus, Catriona McClements, Joyce McKenzie,
and Deborah Morrison

Introduction 322

Therapeutic Inertia 323

Polypharmacy 326

Nonadherence 329

The Patient with Problematic Hypoglycaemia 330

Prescribing in Renal Impairment 333

Prescribing in Liver Disease 337

Prescribing in Cardiovascular Disease 340

Prescribing in Pregnancy 347

Prescribing in the Young 348

Prescribing in the Elderly 349

The Patient with Type 1 Diabetes: a Therapeutic Journey (an Illustrative Case) 350

The Patient with Type 2 Diabetes: a Therapeutic Journey (an Illustrative Case) 351

Future Developments in Prescribing in Diabetes 353

Appendix 357

Index 359

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