TABLE 14.2 Medications Approved by the US Food and Drug Administration for Obesity Treatment8-19
(continued)
Drug (brand name) and available doses
Setmelanotide (Imcivree)
2 mg subcutaneous injection prescibed once daily (ages 12 y and older)
1 mg subcutaneous injection prescribed once daily (ages 6-12 y)
Can titrate up to 3 mg daily
Mechanism of action
MC4R agonist
Restores MC4R activity in the brain and downstream pathways
Only approved for patients with proven POMC deficiency, PCSK1 deficiency, or leptin receptor deficiency
Not approved for polygenic (common) obesity
Oral superabsorbent hydrogel (Plenityd
)
3 capsules prescribed 20- 30 min before each meal (with 500 mL water)
Particles absorb water in stomach and mix with foods
Occupies about 25% of average stomach volume
Diarrhea
Abdominal distension Constipation Gas
Abdominal pain
Abbreviations: BP, blood pressure; GABA, γ-aminobutyric acid; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide 1; MAOI, monoamine oxidase inhibitor; MC4R, melanocortin-4 receptor; PCSK1, proprotein convertase subtilisin/kexin type 1;
POMC, pro-opiomelanocortin; RA, receptor agonist. a
All antiobesity medications are contraindicated in pregnancy and breastfeeding.
b Placebo-subtracted average weight loss with the highest dose at 1 year unless otherwise stated. c Alli is the only FDA-approved over-the-counter weight loss medication.
d Plenity is obtained through a prescription but considered a device, not a medication, which is delivered through capsules but not systemically absorbed.
Appetite regulation involves a complex system of both central and peripheral signals, and this system is further influenced by external factors. Appetite control is not just a matter of increased self-discipline or having the willpower to “eat less.” Antiobesity medications, once termed appetite suppressants, increase weight loss mainly by influencing the various signals involved in appetite regulation which decrease hunger, increase satiety, or reduce hedonic responses to food. Most of the medications’ direct effects work centrally to reduce appetite and increase satiety. Phentermine, for example, increases norepinephrine levels. Topiramate’s mecha- nism for weight loss remains uncertain, but its inhibition of carbonic anhydrase, antagonism of α-amino-3-hydroxy-4-isoxazole-propionic acid kainate (AMPA/ KA) receptors, and activation of γ-aminobutyric acid receptors likely contribute.8 Combination naltrexone and bupropion increases dopamine levels and activates pro-opiomelanocortin (POMC) cells found in the hypothalamus, which in turn activate the melanocortin-4 receptors (MC4R) and shut down feeding.9,20
One of
the newest medications treats patients whose obesity arises from specific genetic causes related to leptin receptor deficiency or POMC deficiency.10
GLP- 1 receptor
agonists improve incretin function, both peripherally by increasing insulin release, suppressing hepatic gluconeogenesis and decreasing glucagon secretion. They also delay gastric emptying and reduce food intake.
CHAPTER 14: Medical and Surgical Interventions 257
Esophageal abnormalities (webs, rings), stricture, prior gastrointestinal surgery
2% at 6 months18
Most common side effects
Hyperpigmentation
Injection site reaction Nausea Vomiting Diarrhea
Abdominal pain Fatigue
Contraindicationsa None
Average weight lossb
23% at 1 year for patients with POMC or PCSK1 deficiency10
9.7% at 1 year for patients with leptin receptor deficiency
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122 |
Page 123 |
Page 124 |
Page 125 |
Page 126 |
Page 127 |
Page 128 |
Page 129 |
Page 130 |
Page 131 |
Page 132 |
Page 133 |
Page 134 |
Page 135 |
Page 136 |
Page 137 |
Page 138 |
Page 139 |
Page 140 |
Page 141 |
Page 142 |
Page 143 |
Page 144 |
Page 145 |
Page 146 |
Page 147 |
Page 148 |
Page 149 |
Page 150 |
Page 151 |
Page 152 |
Page 153 |
Page 154 |
Page 155 |
Page 156 |
Page 157 |
Page 158 |
Page 159 |
Page 160 |
Page 161 |
Page 162 |
Page 163 |
Page 164 |
Page 165 |
Page 166 |
Page 167 |
Page 168 |
Page 169 |
Page 170 |
Page 171 |
Page 172 |
Page 173 |
Page 174 |
Page 175 |
Page 176 |
Page 177 |
Page 178 |
Page 179 |
Page 180 |
Page 181 |
Page 182 |
Page 183 |
Page 184 |
Page 185 |
Page 186 |
Page 187 |
Page 188 |
Page 189 |
Page 190 |
Page 191 |
Page 192 |
Page 193 |
Page 194 |
Page 195 |
Page 196 |
Page 197 |
Page 198 |
Page 199 |
Page 200 |
Page 201 |
Page 202 |
Page 203 |
Page 204 |
Page 205 |
Page 206 |
Page 207 |
Page 208 |
Page 209 |
Page 210 |
Page 211 |
Page 212 |
Page 213 |
Page 214 |
Page 215 |
Page 216 |
Page 217 |
Page 218 |
Page 219 |
Page 220 |
Page 221 |
Page 222 |
Page 223 |
Page 224 |
Page 225 |
Page 226 |
Page 227 |
Page 228 |
Page 229 |
Page 230 |
Page 231 |
Page 232 |
Page 233 |
Page 234 |
Page 235 |
Page 236 |
Page 237 |
Page 238 |
Page 239 |
Page 240 |
Page 241 |
Page 242 |
Page 243 |
Page 244 |
Page 245 |
Page 246 |
Page 247 |
Page 248 |
Page 249 |
Page 250 |
Page 251 |
Page 252 |
Page 253 |
Page 254 |
Page 255 |
Page 256 |
Page 257 |
Page 258 |
Page 259 |
Page 260 |
Page 261 |
Page 262 |
Page 263 |
Page 264 |
Page 265 |
Page 266 |
Page 267 |
Page 268 |
Page 269 |
Page 270 |
Page 271 |
Page 272 |
Page 273 |
Page 274 |
Page 275 |
Page 276 |
Page 277 |
Page 278 |
Page 279 |
Page 280 |
Page 281 |
Page 282 |
Page 283 |
Page 284 |
Page 285 |
Page 286 |
Page 287 |
Page 288 |
Page 289 |
Page 290 |
Page 291 |
Page 292 |
Page 293 |
Page 294 |
Page 295 |
Page 296 |
Page 297 |
Page 298 |
Page 299 |
Page 300 |
Page 301 |
Page 302 |
Page 303 |
Page 304 |
Page 305 |
Page 306 |
Page 307 |
Page 308 |
Page 309 |
Page 310 |
Page 311 |
Page 312 |
Page 313 |
Page 314 |
Page 315 |
Page 316 |
Page 317 |
Page 318 |
Page 319 |
Page 320 |
Page 321 |
Page 322 |
Page 323 |
Page 324 |
Page 325 |
Page 326 |
Page 327 |
Page 328 |
Page 329 |
Page 330 |
Page 331 |
Page 332 |
Page 333 |
Page 334 |
Page 335 |
Page 336 |
Page 337 |
Page 338 |
Page 339 |
Page 340 |
Page 341 |
Page 342 |
Page 343 |
Page 344 |
Page 345 |
Page 346 |
Page 347 |
Page 348 |
Page 349 |
Page 350 |
Page 351 |
Page 352 |
Page 353 |
Page 354 |
Page 355 |
Page 356 |
Page 357 |
Page 358 |
Page 359 |
Page 360 |
Page 361 |
Page 362 |
Page 363 |
Page 364 |
Page 365 |
Page 366 |
Page 367 |
Page 368 |
Page 369 |
Page 370 |
Page 371 |
Page 372 |
Page 373 |
Page 374 |
Page 375 |
Page 376 |
Page 377 |
Page 378 |
Page 379 |
Page 380 |
Page 381 |
Page 382 |
Page 383 |
Page 384 |
Page 385 |
Page 386 |
Page 387 |
Page 388 |
Page 389 |
Page 390 |
Page 391 |
Page 392 |
Page 393 |
Page 394 |
Page 395 |
Page 396 |
Page 397 |
Page 398 |
Page 399 |
Page 400 |
Page 401 |
Page 402 |
Page 403 |
Page 404 |
Page 405 |
Page 406 |
Page 407 |
Page 408 |
Page 409 |
Page 410 |
Page 411 |
Page 412 |
Page 413 |
Page 414 |
Page 415 |
Page 416 |
Page 417 |
Page 418
