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 Metabolism and Elimination 6
Drug Development and Clinical Trials 7
Drug Licensing of Antidiabetic Drugs 12
Development and Licensing of Insulin 14
Development and Approval of Biosimilar Insulin 16
Pharmacovigilance 19
Pharmacoeconomics 21
Future Developments in Diabetes Clinical Pharmacology 26
2 Metformin 30
Joseph Timmons and James Boyle
Introduction 30
Pharmacology 32
Mechanism of Action 32
Glycaemic Efficacy 36
Safety and Side Effects 37
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
Renal Outcomes 89
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
Renal Outcome Trials 110
Heart Failure Outcome Trials 116
SGLT2 Inhibitors in Type 1 Diabetes 119
Use of SGLT2 Inhibitors in Other Diseases 123
Dare- 19 123
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
Hypoglycaemia and Human Insulin 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
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
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
